GMP Question and Answers including In process QA (IPQA) checks - interview questions & Answer

GMP Question and Answers       

What is GMP?

Good manufacturing practice (GMP) is a system for ensuring that products are consistently produced and controlled according to quality standards. It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product. The main risks are: unexpected contamination of products, causing damage to health or even death; incorrect labels on containers, which could mean that patients receive the wrong medicine; insufficient or too much active ingredient, resulting in ineffective treatment or adverse effects. GMP covers all aspects of production; from the starting materials, premises and equipment to the training and personal hygiene of staff. Detailed, written procedures are essential for each process that could affect the quality of the finished product. There must be systems to provide documented proof that correct procedures are consistently followed at each step in the manufacturing process - every time a product is made. WHO has established detailed guidelines for good manufacturing practice. Many countries have formulated their own requirements for GMP based on WHO GMP. Others have harmonized their requirements, for example in the Association of South-East Asian Nations (ASEAN), in the European Union and through the Pharmaceutical Inspection Convention.

Why is GMP important?

Poor quality medicines are not only a health hazard, but a waste of money for both governments and individual consumers.

Poor quality medicines can damage health

A poor quality medicine may contain toxic substances that have been unintentionally added.
A medicine that contains little or none of the claimed ingredient will not have the intended therapeutic effect.

GMP helps boost pharmaceutical export opportunities

Most countries will only accept import and sale of medicines that have been manufactured to internationally recognized GMP. Governments seeking to promote their countries' export of pharmaceuticals can do so by making GMP mandatory for all pharmaceutical production and by training their inspectors in GMP requirements.

Is GMP necessary if there is a quality control laboratory?

Yes. Good quality must be built in during the manufacturing process; it cannot be tested into the product afterwards. GMP prevents errors that cannot be eliminated through quality control of the finished product. Without GMP it is impossible to be sure that every unit of a medicine is of the same quality as the units of medicine tested in the laboratory.

Can manufacturers afford to implement GMP?

Yes. Making poor quality products does not save money. In the long run, it is more expensive finding mistakes after they have been made than preventing them in the first place. GMP is designed to ensure that mistakes do not occur. Implementation of GMP is an investment in good quality medicines. This will improve the health of the individual patient and the community, as well as benefiting the pharmaceutical industry and health professionals. Making and distributing poor quality medicines leads to loss of credibility for everyone: both public and private health care and the manufacturer.

What are the 10 golden rules of GMP ?

Golden Rule#01	Get the facility design right from the start
Golden Rule#02	Validate processes
Golden Rule#03	Write good procedures and follow them
Golden Rule#04	Identify who does what
Golden Rule#05	Keep good records
Golden Rule#06	Train and develop staff
Golden Rule#07	Practice good hygiene
Golden Rule#08	Maintain facilities and equipment
Golden Rule#09	Build quality into the whole product lifecycle
Golden Rule#10	Perform regular audits

Golden Rule # 01

Get the facility design right form the start

Every food, drug, and medical device manufacturer aims to operate their business in accordance with the principles of Good Manufacturing Practice (GMP). It’s much easier to be GMP compliant if the design and construction of the facilities and equipment are right from the start. It’s important to embody GMP principles and use GMP to drive every decision.

‘Sometimes you need to step back and reconsider the whole production area’

Facility layout

Lay out the production area to suit the sequence of operations. The aim is to reduce the chances of cross contamination and to avoid mix-ups and errors. For example, don’t have final product passing through or near areas that contain intermediate products or raw materials. A logical and well-planned layout will improve productivity. Sometimes you need to step back and reconsider the whole production area rather than applying quick fix solutions.

Aim to: ♣ remove unnecessary traffic in the production area which could result in a hazardous environment
♣ segregate materials, products, and their components to minimize confusion and potential for mix-ups and errors.

Example: A company, through poor planning, failed to keep the product manufacturing process linear. As the product moved through the factory, it was zigzagged from one area to another. This meant that near-final product was exposed to early-stage product with the potential of contamination. Before making any changes, the company should have stepped back and reviewed the layout as a whole.

Environment

It’s important to control the air, water, lighting, ventilation, temperature, and humidity within a plant so that it does not impact product quality. You should design facilities to reduce the risk of contamination from the environment.

Make sure that: ♣ lighting, temperature, humidity and ventilation are appropriate ♣ interior surfaces (walls, floors and ceilings) are smooth, free from cracks and do not shed particulate matter ♣ interior surfaces are easy to clean  ♣ pipe work, light fittings, and ventilation points are easy to clean ♣ drains are sized adequately and have trapped gullies.

Equipment

Design, locate, and maintain equipment to suit its intended use.

Make sure that equipment is: ♣ easy to repair and maintain ♣ designed and installed in an area where it can be easily cleaned ♣ suitable for its intended use ♣ not reactive, additive or absorptive ♣ calibrated at defined intervals (if necessary) ♣ clearly labelled.

Golden Rule # 02

Validate processes

It’s one thing to design and construct state of the art facilities and equipment, but how do you ensure that it’s operated in a controlled manner? This is where validation comes into play. To prove that equipment and processes consistently do what they are supposed to do, testing and documentation is required. Consistent performance is the key to maintaining safety and effectiveness of every product and enhances a company’s reputation for quality and reliability.

Validation by definition, validation is: "Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes."

It’s a GMP requirement to prove control of the critical aspects of certain operations. New facilities and equipment, as well as significant changes to existing systems, require validation. All validation activities should be well planned and clearly defined. This is usually by means of a Validation Master Plan, or VMP. Before you get to this stage consider all the critical parameters that may be affected and impact product quality; what happens if the stirring speed is changed? How does this affect temperature or pH? Once this is complete, define the testing and documentation required.

Validation usually involves:

♣ Installation Qualification, or IQ, which is testing to verify that the equipment is installed correctly
♣ Operational Qualification, or OQ, which is testing to verify that the equipment operates correctly
♣ Performance Qualification, or PQ, which is testing to verify that product can be consistently be produced to specification.

A protocol describing each test and the acceptance criteria should be prepared, and once the testing is complete, a report written.

Change control

Once testing is complete and the equipment or process is known to be controlled, it’s important to maintain its ‘validated state’. Achieve this by correctly following written procedures, and properly maintaining and calibrating equipment. If a change to the validated state is required then it must be subject to change control. A change control system should be in place to document all changes to facilities, equipment, or processes that may have an impact on product quality. You should evaluate the impact of the change and define the extent of re-validation.

Example: A computer system was validated after it was first installed on site. Some years later an auditor discovered that changes had been made to the system. No re-validation work had been performed and the system was no longer in its validated state. How did the company know that the system was operating in a controlled and consistent manner? The answer is they didn’t. The oversight was due to a weak change control system that allowed changes to be made without formal evaluation and re-validation.

Golden Rule # 03

Write good procedure and follow them

Think about what happens in a workplace if written procedures are not available. People rely on longer-term employees to tell them how to do things and then do their job from memory. This is fine for a company making garden pots, but not so good when the products you are making can cause death! In the food, drug and medical device industry it’s critical that good procedures are in place to ensure a controlled and consistent performance; it’s an essential part of GMP. Procedures should be clear, concise, and logical. Consider hiring a professional technical writer to do the job. Unlike permanent employees they know how write well and will perform usability tests to ensure that documents work. Having an independent party reviewing your procedures also leads to process improvements.

Documentation requirements

The following documents are typical in the food, drug, and medical device industry:

♣ Specifications: These detail the requirements with which products and materials have to conform, i.e. they serve as a basis of quality evaluation ♣ Operating Instructions: These detail material and equipment requirements and describe the steps to complete a task ♣ Operating Procedures: These give direction for performing certain tasks and provide higher-level instruction than operating instructions. ♣ Records: These provide a history of each batch and provide a mechanism to check that you are following operating procedures and instructions.

‘Procedures should be clear, concise, and logical’

Writing good procedures

Outline the task before you begin writing the procedure. Create a brief breakdown of the important steps and key points related to the task; a flow chart is a useful tool. Remember that people don’t usually read procedures from start to finish; they tend to scan the document for key words.

Break the procedure into chunks and use: ♣ headings ♣ tables ♣ bullet points ♣ diagrams.

This makes the information easier to digest and follow.

When writing procedures try to visualise the person that will use it. Use language they will understand and don’t include too much or too little information. You can increase the readability of your procedures by using simple sentences and by writing in a conversational style. Use an online tool such as http://www.onlineutility.org/english/readability_test_and_improve.jsp to test readability.

Aim at a readability score that matches the educational level of the person using the document. You can also check that the procedure is usable by performing a ‘usability test’. Print out two copies of the procedure and ask someone unfamiliar with the task to follow it. Mark up the second copy with notes about where they found the document confusing. This will highlight problems with the document and is a great learning experience for the writer.

It is a GMP requirement to regularly review documentation to ensure that it’s up to date. Most companies have a three-year review cycle for their documents however this can be set according to the likelihood of change in the process that the document relates to.

Some operators resist following procedures because they think they have a ‘better’ way of working.

Introduce a “Better Operating Procedures” system within the work group where the team meets to discuss procedures that are not followed. Allow operators to suggest how they think a task should be performed and act on it

Following procedures

It’s all very well to have great written procedures in place but to ensure a controlled and consistent performance they need to be followed; it’s a GMP requirement. Frequently, the steps described in a written procedure may not appear to be the most efficient way of working. Taking shortcuts may save time or make the task easier, but you should never deviate from a written procedure without the approval of a supervisor or the Quality Department.

There are two main reasons for this: ♣ Many shortcuts may create pitfalls that can be costly in the end. ♣ Each step in a procedure has been included for a purpose.

Even though the sense of a particular step may not be directly apparent, it may be there as a check for another stage of the process. Ideas for improvement should always be encouraged but don’t change procedures without assessing the impact on the entire process.

Golden Rule # 04

Identify who does what

All employees should clearly understand what they have to do each day. It avoids misunderstandings and minimises the risk to product quality.

You should create a job description for each role to define: ♣ job title ♣ job objective ♣ duties and responsibilities ♣ skill requirements. There should be no gaps or overlaps in responsibilities. Create an organizational chart and display it on the intranet or a local notice board. This way everyone in the organization can see who does what.

Some areas that are vulnerable to overlap include: ♣ cleaning ♣ validation ♣ calibration. When preparing procedures for these areas carefully consider and define the responsibilities. It’s also vital that employees are trained to undertake a task that they are assigned responsibility to; this is covered further in Golden Rule #6.

Example: During a validation batch a series of samples were not taken as the operators thought that validation staff would take them, whilst validation thought that the operators would take them. The sampling responsibilities should have been detailed in sampling procedures and the validation documentation.

Golden Rule # 05

Keep good records

Good records enable you to track all activities performed during batch manufacture from the receipt of raw materials, to the final product release; they provide a history of the batch and its distribution. It is an essential part of GMP to keep accurate records, and during an audit, it helps convey that you are following procedures. It also demonstrates that processes are known and under control.

‘If it’s not written down then it didn’t happen!’

Good record keeping

Follow these guidelines to ensure that good record keeping is part of your everyday culture:

Record all necessary information immediately upon completion of a task.

Never trust your memory or write results on loose pieces of paper.

Write your name legibly in ink. Remember that by signing records you are certifying that the record is correct and that you have performed the task as per the defined procedure.

Draw a single line through any mistakes, and initial and date the correction. Include a reason for the correction at the bottom of the page.

Record details if you deviate from a procedure. Ask your supervisor or the Quality Department for advice should a deviation occurs.

Don't document someone else's work unless you are designated and trained to do so.

Never assume that undocumented work has been properly completed – if it’s not written down then it didn’t happen!

Tip

Signature fatigue is a problem in the pharmaceutical world. Employees are asked to sign so many records and can become complacent about what their signature actually means. Review your procedures to reduce the number of signatures to critical steps only. Include a ‘checked by’ signature when it’s required by a predicate rule.

Retention requirements

You should keep records for every stage of the manufacturing process.

Some required records include: ♣ product master records ♣ batch or manufacturing records ♣ material / component control records ♣ personnel records ♣ training records ♣ equipment logs ♣ cleaning logs.

Keep documents that form GMP records for one year past the expiry date of the product or three years past the distribution date of the product, whichever comes later. You can define your own retention period for other documents and files. If you follow these guidelines, you will easily be able to examine each step of the manufacturing process should you need to.

Golden Rule # 06

Train and develop staff

To meet GMP requirements it’s essential to have the right people to do the right job. Do your employee’s have the skills and knowledge to complete their job? Have you equipped them with the right tools? If so, then you can be proud that your people are doing the right thing to make GMP a culture.

‘Companies need people who know how to the job right first time, every time’

Training

You should provide training for all employees whose duties take them into production areas or laboratories, and whose activities could affect the quality of the product. This includes basic training on the theory and practice of GMP as well as specific training relative to their role. Sometimes it’s unavoidable to take an untrained visitor into a production area. If this happens, provide them with some information in advance, particularly relating to personal hygiene, and closely supervise them at all times.

It’s also important to ensure that training requirements are highlighted as part of the change control system. If you install a new piece of equipment then employees must know how to use it. You should check that training is complete during validation or add it as a separate change control task. The same also applies for updates to procedures or instructions. Usually the document control process will define the training requirements for document updates.

Demonstrating job competence

Employees must demonstrate their job competence every day by producing quality products in a safe and efficient manner. Companies need people who know how to do the job right the first time, every time. Annual performance reviews are also a great way to formally discuss an employee’s development and performance.

It’s a great way to review what the employee has achieved and to identify any gaps or areas for further development.

Areas to discuss include: ♣ key performance indicators ♣ work plans ♣ roles and responsibilities ♣ position descriptions ♣ training ♣ financial compensation. Document the outcome so that you can review it later.

Golden Rule # 07

Practice good hygiene

It’s critical to reduce the risk of product contamination to a minimum by putting in place a sanitation program. Develop a program to meet the standards of cleanliness necessary for the product. As an example, you would have different cleaning standards for sterile products used in an operating theatre as opposed to products that you inject into your bloodstream. The fight against contamination is a constant battle and is one that requires the attention of every single employee, every day.

To convince staff of the importance of washing their hands after toileting, ask the microbiology department to take fingerprint samples from each operator after they have washed their hands. They can then see how much bacteria is present on their ‘clean’ hands.

Keep these practices in mind:

♣ ALWAYS practice good personal hygiene by washing your hands and wearing the required protective garments. ♣ Inform your supervisor if you are ill; you may not be allowed to enter the manufacturing area until you are well again. ♣ Minimize contact with product or product contact surfaces and equipment. ♣ NEVER eat, drink, smoke or chew in manufacturing areas. ♣ ALWAYS follow cleaning and sanitation procedures. ♣ Report any condition that may cause product contamination. ♣ Remove trash and waste materials, and store appropriately. These practices are nothing more than common sense and are your best defense to reduce the risk of product contamination.

Golden Rule # 08

Maintain facilities and equipment

It’s important to have a maintenance schedule for facilities and equipment. Regular equipment maintenance prevents equipment breakdowns, which can be costly. It also reduces the risk of product contamination and maintains the ‘validated state’ of the facility or equipment. Sometimes an unexpected event may affect the facility or equipment and under such circumstances, you need to carry out repairs immediately.

You should have written procedures for all scheduled and emergency maintenance. These should detail who does the work, the tasks involved, and define any lubricants, coolants, cleaning agents etc. required. It’s also a GMP requirement to have a maintenance schedule in place with the frequency determined by the criticality of the equipment.

Tip

When writing maintenance procedures consider whether the work can be performed outside the manufacturing area so that it doesn’t affect the remainder of the facility. If this can’t be achieved, remember to detail the cleaning requirements to get the plant back to a GMP standard. Maintenance Records GMP requires you to keep accurate records relating to maintenance activities.

Use equipment logs to record information such as: ♣ when the equipment was last used ♣ what is was used for ♣ when it was cleaned ♣ when it was last inspected or repaired ♣ when it was last calibrated

Walk around your plant and check all the calibration stickers you can see. If they are out of date then your maintenance process is not being controlled properly

Golden Rule # 09

Design quality into the whole product lifecycle

By working the in food, drug, and medical device industry you know that the health and safety of the customer depends on the quality of the product. The QC department can only inspect for quality so it’s critical that you build quality into the product lifecycle. Every step in the product lifecycle requires effective controls to assure product quality. Here are four critical areas:

Controlling Components

Check all materials and components when they enter the plant to ensure they meet the defined specifications. Identify components and store them in a quarantine area for sampling and testing. All materials and components must be approved prior to release for manufacturing, or if rejected, they must be identified and stored in a secure area to prevent accidental use.

Controlling the Manufacturing Process

Establish records and procedures to ensure that employees perform the same job every time.
Each product must have: ♣ A master record that outlines the specifications and manufacturing procedures. ♣ Individual batch or history records to document conformance to the master record. ♣ Written schedules and procedures for cleaning and maintaining the equipment and areas.

Packaging and Labelling Controls

Packaging and labelling are areas where mix-ups and errors occur. To enable traceability, assign a batch or lot number to each product. Before a new batch or lot is processed, inspect packaging and labelling areas to ensure that it contains no material from a previous batch. Follow all procedures and carefully document your work.

Holding and Distribution Controls

The company must have controls against contamination, mix-up, and errors. Provide separate areas for quarantine and finished product testing. Prepare procedures for handling and storage of products and distribution records to help trace shipments.

Golden Rule # 10

Perform regular audits

Audits must be conducted to assess whether you are following the GMP rules. External bodies such as the Food and Drug Administration (FDA) or the Therapeutic Goods Association (TGA) will conduct these audits. You should also conduct in-house audits, or self-inspections, to ensure GMP compliance. A ‘Self Audit Checklist’ is provided below. It’s a good practice to undertake a self-audit a few times a year and to target different manufacturing areas and departments each time.

Tip

You’ll need a Corrective Action Preventative Action (CAPA) system to manage and fix anything found during an audit.

Self-Audit Checklist

Written Procedures

θ Are there procedures that provide "step by step instructions" to perform my job?

θ Do I know and understand these procedures and do I carefully follow them?

θ Do I regularly review my procedures to make sure they are accurate and up-to-date?

θ Do I refrain from deviating from my written procedures? When I see an easier or better way to do my job do I discuss this with my supervisor?

Job Competence

θ Do I have the necessary education, training, and on-the-job experience to perform my assigned function?

θ Have I identified and acquired the necessary skills (i.e. been trained) that relate to my job?

θ Do I perform my job right the first time and every time?

Documentation and Validation

θ Do I carefully document my work by recording all necessary information immediately?

θ Do I sign my name legibly and in ink, when and where a signature is required?

θ If required, do I mark down the date and the time I started or completed the job?

θ Do I check and double-check all critical operations to make sure there are no errors?

Sanitation and Cleanliness

θ Do I always practice good personal hygiene?

θ Do I always wear the proper garments in the workplace? Do I wear the garments correctly?

θ Are my equipment and tools clean? Do I store them in the proper place?

θ Do I report any conditions in the plant or equipment that could be potential sources of product contamination?

Maintenance of the Workplace

θ Is there adequate space in my work area to safely and effectively perform my job?

θ Do I minimize the chance of product contamination, mix-ups, and errors by helping to control the plant environment?

θ Do I perform routine maintenance on my equipment? Do I check to see if my measuring and testing equipment is calibrated?

θ Do I keep an accurate equipment log? Do I promptly report any maintenance problems to the supervisor? Quality Control

θ Do I carefully control the components used in the manufacture of our products?

θ Do I pay close attention to the lot numbers assigned to components and finished products?

θ Do I know and understand what responsibility the Quality Assurance/Quality Control Department has for assuring Product Quality?

θ Do I know and understand my responsibility to build quality into our products?

If you have answered "no" to any of these questions, then raise a corrective action. Auditing is an important tool to help evaluate your progress toward the goals of GMP. Remember, all employees have a personal responsibility to evaluate how closely they are working to the standards of GMP. If you have answered "yes" to these personal audit questions, your work practices are compliant with the requirements of GMP.

Sources Links used within this document are prone to change. Please refer to the appropriate source for the most recent information. We endeavor to keep an up-to-date record of information at www.pharmout.net

In process QA (IPQA) checks - interview questions & Answer Q. How many Tablets shall be taken for checking friability?

Ans: For tablets with unit mass equal or less than 650 mg, take  sample of whole tablets corresponding to 6.5g.For tablets with unit mass more than 650mg,take a sample of 10 whole tablets.

Q. What is the formula for calculating weight loss during friability test?

Ans: %Weight loss =  Initial Weight - Final Weight  X 100                                                 Initial  Weight

Q. What is the pass or fail criteria for friability test?

Ans: Generally the test is run for once. If any cracked, cleaved or broken tablets present in the tablet sample after tumbling, the tablets fails the test. If the results are doubtful, or weight loss is greater than the targeted value, the test should be repeated twice and the mean of the three tests determined. A mean weight loss from the three samples of not more than 1.0% is considered acceptable for most of the products.

Q. What is the standard number of rotations used for friability test?

Ans: 100 rotations

Q. What is the fall height of the tablets in the friabilator during friability testing?

Ans: 6 inches. Tablets falls from 6 inches height in each turn within the apparatus.

Q. Why do we check hardness during in process checks?

Ans: To determine need for the pressure adjustments on the tableting machine. Hardness can affect the disintegration time. If tablet is too hard, it may not disintegrate in the required period of time. And if tablet is too soft it will not withstand handling and subsequent processing such as coating, packing etc.

Q. What are the factors which influence tablet hardness?

Ans: 1.compression force         2.Binder quantity(More binder more hardness)         3.Moisture content

Q. Which type of tablets are exempted from Disintegration testing?

Ans: Chewable Tablets

Q. Which capsule is bigger in size - size '0' or size '1'?

Ans: '0' size

Q. What is the recommended temperature for checking DT of a dispersible tablet?

Ans: 25 ±10C (IP) & 15 – 250C (BP)

Q. What is mesh aperture of DT apparatus ?

Ans: 1.8 -2.2mm (#10)

Q. List out the appearance defects of tables during compression activity ?

Sr.No. Appearance Defects 1. Capping:- ‘Capping’ is the term used, when the upper or lower segment of the tablet separates horizontally, either partially or completely from the main body of a tablet and comes off as a cap, during ejection from the tablet press, or during subsequent handling. 2. Lamination / Laminating:- Definition: ‘Lamination’ is the separation of a tablet into two or more distinct horizontal layers. 3. Sticking/filming: ‘ Sticking’ refers to the tablet material adhering to the die wall. Filming is a slow form of sticking and is largely due to excess moisture in the granulation. 4. Cracking:-  Small fine cracks observed on the upper and lower center surface of the tablets, or very rarely on the side wall are referred to as cracks. 5. Chipping:- ‘ Chipping’ is defined as the breaking of tablet edges, while the tablet leaves the press or during subsequent handling and coating operation. 6. Mottling:‘ Mottling’ is the term used to describe an unequal distribution of colour on a tablet. 7. Double Impression: ‘ Double impression’ involves only those punches,which have a monogram or other engraving on them.

Q. What is the pass/fail criteria for disintegration test?

Ans: If one or two tablets/capsules fails to disintegrate completely, repeat the test on another 12 additional dosage units. The requirement is meet if not fewer than 16 out of 18 tablets/capsules tested are disintegrated completely.

Q. What is the recommended storage conditions for empty hard gelatin capsules?

Ans: 15 - 250C & 35 -55% RH

Q. Which method is employed for checking “Uniformity of dosage unit”?

Ans:  A.)    Content uniformity B.)        Weight Variation Weight variation is applicable for following dosage forms; Hard gelatin capsules,uncoated or film coated tablets,containing 25mg or more of a drug substance comprising 25% or more by weight of dosage unit.

Q. What is the recommended upward and downward movement frequency of a basket-rack assembly in a DT apparatus?

Ans: 28 – 32 cycles per minute.

Q. When performing the ‘uniformity of weight’ of the dosage unit, how many tablet/capsule can deviate the established limit?

Ans: Not more than two of the individual weights can deviates from the average weight by more than the percentage given in the pharmacopeia,and none can deviates more than twice that percentage. Weight Variation limits for Tablets         IP/BP Limit       USP 80 mg or less 10% 130mg or less More than 80mg or Less than 250mg 7.5% 130mg to 324mg 250mg or more 5% More than 324mg Weight Variation limits for Capsules IP Limit Less than 300mg 10% 300mg or More 7.5%

Q. What needs to be checked during inprocess QA checks?

Ans:  a.) Environmental Monitoring b.) Measured values obtained from the process equipment (ex: temperature, RPM etc.) c.) Measured values obtained from persons (ex: timings, entries etc.) d.) Process attributes (Ex: weight, hardness, friability etc.)

Q. What precautions shall be taken while collecting in process samples?

Ans: While collecting in process samples, avoid contamination of the product being sampled (Don’t collect samples with bare hands) & avoid contamination of sample taken.

Q. In a tablet manufacturing facility ‘positive’ pressure is maintained in processing area or service corridors?

Ans: In tablet manufacturing facilities, pressure gradients are maintained to avoid cross contamination of products through air. Usually service corridors are maintained under positive pressure with respect to processing areas.

Q. If sticking observed during tablet compression what may the probable reason for the same?

Ans:  1.If the granules are not dried properly sticking can occur. 2.Too little or improper lubrication. 3.Too much binder 4.Hygroscopic granular

Q. What checks shall be carried out, while calibrating  DT apparatus?

Ans: While calibrating DT apparatus, following checks shall be performed. 1.)           Number of strokes per minute (Limit:29-32 cycles/min) 2.)           Temperature by probe & standard thermometer            (Limit:  37 ± 1 OC).     3).   Distance travelled by basket (Limit:53 -57mm)

Q. Why difference pressure gradients are maintained?

Ans: In tablet manufacturing facilities, pressure gradients are maintained to avoid cross contamination of products through air. Usually processing areas are maintained under positive pressure with respect to service corridors.

Q. What is In process checks?

Ans: In process checks are  checks performed during an activity,In order to monitor and,if necessary,to adjust the process to ensure that product confirms to its specification.

Q. What is the difference between disintegration and dissolution?

Ans: Disintegration is a disaggregation process, in which an oral dosage form falls apart in to smaller aggregates.(Disintegration time is the ‘break up’ time of a solid dosage form). Where as dissolution is a process by which solid substance enters in the solvent to yield a solution.It is controlled by the affinity between the solid substance and the solvent. In other word disintegration is a subset of dissolution.

Q. What is the difference between calibration and Validation?

Ans: Calibration is a demonstration that, a particular Instrument or device produces results within specified limits by comparisons with those produced by a reference or traceable standard over an appropriate range of measurements. Where as Validation is a documented program that provides high degree of assurance that a specific process, method or system consistently produces a result meeting pre-determined acceptance criteria. In calibration performance of an instrument or device is comparing against a reference standard. But in validation such reference standard is not using. Calibration ensures that instrument or measuring devices producing accurate results. Whereas validation demonstrates that a process, equipment, method or system produces consistent results (in other words, it ensures that uniforms batches are produced).

Q. Why do we calibrate a qualified equipment/instrument on definite intervals?

Ans: An equipment or instrument can ‘drift’ out of accuracy between the time of qualification and actual use.So it is recommended to calibrate and recalibrate the measuring devices and instruments on predetermined time intervals, to gain confidence on the accuracy of the data.

Q. Why do we  consider three consecutive runs/batches for process validation? Why not two or four?

Ans: The number of batches produced in the validation exercise should be sufficient to allow the normal extent of variation and trends to be established and to provide sufficient data for evaluation and reproducibility. ·       First batch quality is accidental (co-incidental), ·       Second batch quality is regular (accidental), ·       Third batch quality is validation(conformation). In 2 batch we cannot assure the reproducibility of data,4 batches can be taken but the time and cost are involved.

Q. Position of oblong tablets to be placed in hardness tester to determine the hardness? Lengthwise / widthwise?

Ans: Position of oblong tablets should be length wise because the probability of breakage is more in this position.                         PHARMACOVIGILANCE

phar·ma·co·vig·i·lance                   ˌfärməkōˈvijələns/       noun: pharmacovigilance;   noun: pharmaco-vigilance

The practice of monitoring the effects of medical drugs after they have been licensed for use, especially in order to identify and evaluate previously unreported adverse reactions.

"The partnership hopes to develop diagnostic tools to improve pharmacovigilance"

Pharmacovigilance

Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. WHO established its Programme for International Drug Monitoring in response to the thalidomide disaster detected in 1961. Together with the WHO Collaborating Centre for International Drug Monitoring, Uppsala, WHO promotes PV at the country level. At the end of 2010, 134 countries were part of the WHO PV Programme. The aims of PV are to enhance patient care and patient safety in relation to the use of medicines; and to support public health programmes by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines.

Pharmacovigilance is responsible for monitoring the safety of medicines in normal clinical use and during clinical trials. In the light of the experience acquired and following an assessment by the Commission of the Union system of pharmacovigilance, it has become clear that it is necessary to take measures in order to improve the operation of Union law on the pharmacovigilance of medicinal products for human use. Regulation (EU) No 1235/2010 and Directive 2010/84/EU introduced new legislation on pharmacovigilance. The marketing authorization holder should be responsible for continuously monitoring the safety of its medicinal products for human use, for informing the authorities of any changes that might have an impact on the marketing authorization, and for ensuring that the product information is kept up-to-date. Marketing authorization holders (MAH) record all suspected adverse reactions occurring in the European Union or in the third countries, and which are brought to their attention spontaneously by the patients or their health care, or occurring in the context of post-authorization study. For all medicinal products is mandatory to maintain a pharmacovigilance system master file (PSMF). According to the Legislative Decree 219/2006 the MAH must submit to the competent authorities the information on suspected adverse reactions of a medicinal product, in form of a periodic safety update reports (PSURs).

Why 70% Isopropyl Alcohol (IPA) is used as Disinfectant in Pharmaceuticals?

Know why 70% isopropyl alcohol (IPA solution) is used for disinfection of hands and equipment surface instead of 100% in pharmaceuticals.

70% isopropyl alcohol is most commonly used disinfectant in pharmaceutical industries. The important thing is that only 70% solution of isopropyl alcohol acts as a disinfectant killing all surface microorganisms. It is used to disinfect hands and equipment surface in pharmaceuticals.

70 % isopropyl alcohol solution kills microorganisms by dissolving plasma membrane of the cell wall. Plasma membrane of gram negative bacteria consist of thin layer of peptidoglycon that easily destroyed by the alcohol. Therefore, 70 percent iso propyl alcohol is known as pharmaceutical alcohol.

Water is also required to denature the proteins of cell membrane and acts as a catalyst in the reaction. Contact time of the alcohol with the organism also play an important role. A 70% solution of alcohol takes more time in evaporation from the surface, increasing the contact time. Therefore, 70% isopropyl alcohol fulfills the both requirements.

100% isopropyl alcohol coagulates the protein instantly creating a protein layer that protects the remaining protein from further coagulation. Due to this organism is not killed but remains in dormant stage. While 70% isopropyl alcohol solution penetrates in the cell wall at slower rate and coagulates the all protein of the cell wall and microorganism dies.

Thus 70% IPA solution in water is more effective then 100% absolute alcohol and have more disinfectant capacity.

Following points should be considered while using 70% Isopropyl Alcohol:

1. 70% Isopropyl Alcohol should be prepared on daily basis.

2. Preparation should be done in controlled area by production.

3. Freshly prepared 70 % isopropyl alcohol solution should be used.

4. For the preparation of the 70% IPA, purified water should be used.

5. The bulk container (used for distribution) of the 70% IPA should have the label with the details like name, prepared on, prepared by and checked by. While the small container label should have the details like name, prepared on and prepared by.

6. The prepared 70 % IPA should be analyzed chemically and microbiologically (by membrane filtration method).

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