FDA regulated industries Archives -

Terminology for Inspected Material (GMP, ISO 13485)

Pharmaceutical sampling

Q: There is often confusion with the labeling of purchased materials after they have been “inspected, tested and/or verified” according to good manufacturing practice (GMP)
requirements. Once out of quarantine, are purchased materials labeled as accepted, approved or released? I’ve had auditors and inspectors tell me all three.

A: Either term (accepted, approved, or released) is appropriate and commonly used. It would appear that the auditors are voicing an opinion and shouldn’t be. Neither ISO 13485:2003: Medical devices — Quality management systems — Requirements for
regulatory purposes or FDA’s quality system regulation (QSR) specify what language is to be used.

ISO 13485:2003, clause 7.5.3.3 status identification, states:

“The organization shall identify the product status with respect to monitoring and measurement requirements. The identification of product status shall be maintained throughout production, storage, installation and servicing of the product to ensure that only product that has passed the required inspections and test … is dispatched, used or installed.”

FDA 21 CFR 820.86 acceptance status requires:

“Each manufacturer shall identify by suitable means the acceptance status of product, to indicate the conformance or nonconformance of product with acceptance criteria. The identification of acceptance status shall be maintained throughout manufacturing, packaging, labeling, installation, and serving of the product to ensure that only product which has passed the required acceptance activities is distributed, used, or installed.”

The requirement should be clear for purchased materials: identify so that only those materials that passed acceptance activities are allowed to be used. Neither the standard or regulation states how the material is to be identified. That is up to the manufacturer to define in its operating procedure(s).

My personal recommendation is to use the terms “accept/reject” at receiving and during in-process, then use the terms “release/hold” to mean the final product is or is not to be released for distribution. But any similar terms are fine as long as they are consistently used throughout the quality system and personnel understand the requirement that they can only use product that passed their acceptance activities.

Jim Werner
Voting member to the U.S. TAG to ISO TC 176 Quality Management and Quality Assurance
Medical Device Quality Compliance (MDQC), LLC.
ASQ Senior Member
ASQ CQE, CQA, RABQSA Lead QMS Assessor

For more on this topic, please visit ASQ’s website.

Establishing and Maintaining a CAPA System

Q: We have a Corrective Action and Preventative Action (CAPA) system, and we find that CAPAs are almost always completed late — even though we do have an extension request form for CAPAs, and the system sends automated reminders to employees in advance.

What can we do to resolve this issue and avoid late CAPAs?

A: I will answer this question based on the information provided.

1. Does the CAPA system rank the CAPA based on risk? If not, each CAPA should be ranked either high, medium, or low.

High risks generally mean that the problem behind the CAPA could have a negative affect on the business and put it at risk. For example, in the medical device industry, a high risk CAPA could include a regulation violation, something that can harm a device user or patient, or issues that could result in legal action against the company.

2. Does the CAPA system have a way to involve top management? If not, it should — especially if timely corrective action is not being taken in instances of high risk CAPAs.

3. Does the management review process include a statistical analysis of the time it takes to complete CAPAs?

Often, reports to management include the number of CAPAs greater than 90-days old and greater than 180-days old. In addition to reporting on the number of open CAPAs, also report on the number of CAPAs completed by the due date and the number of CAPAs that are overdue (past the original, assigned completion date).

It is a good idea to also convert these numbers into percentages to make data digestible and to allow for comparison making.

4. Next, discuss with management (if possible) to consider consequences for employees if company problems that result in a CAPAs are not addressed in a timely manner.

With this approach, proceed with caution. You must make certain that the CAPA system is robust. Not every little problem is a CAPA. A good way to weed out the CAPAs from the non-CAPAs is to ask: is this an issue that requires an investigation into the root cause? And, does this problem require corrective action to fix it? If the answers are yes, then it is probably a CAPA.

5. You may want to consider benchmarking how other organizations structure their CAPA system and look to guidance documents for help. The Global Harmonization Task Force published a guidance document help establish CAPA systems. It is for the medical device industry, but it can be applied elsewhere.

Jim Werner
Voting member to the U.S. TAG to ISO TC 176
Medical Device Quality Compliance (MDQC), LLC.
ASQ Senior Member
ASQ CQE, CQA, RABQSA Lead QMS Assessor

For more about this topic, please visit ASQ’s website.

Z1.4 and Z1.9 in Micro Testing and API Chemical Analysis

Chemistry, micro testing, chemical analysis, sampling

Q: I work at a cosmetics manufacturing company that produces sunscreen in bulk amounts. When we make 3,000 kg of sunscreen, we will use that in 10,000 units of final sunscreen products which will weigh 300 g each.

How many samples do I need to collect from the 10,000 units to pass the qualification?

The products need to pass both attribute and variable sampling tests such as container damage, coding error, micro testing, and Active Pharmaceutical Ingredients (API) failure. Almost 100 percent of final products were inspected for appearance error, but a small number of them should be measured for micro testing and API chemical analysis.

For Z1.4-2008: Sampling Procedures and Tables for Inspection by Attributes, we have to collect a sample of 200 (lot size of 3,201-10,000; general inspection level II; acceptable quality level 4.0 L), and more than 179 should pass for qualification.

For Z1.9-2008: Sampling Procedures and Tables for Inspection by Variables for Percent Nonconforming, we have to collect a sample of 25 (lot size of 3,201-10,000; general inspection level II; acceptable quality level 4.0, L), to meet the requirement of 1.12 percent of nonconformance.

Which sampling plan should we follow for micro testing and API chemical analysis?

A: If the micro test is pass/fail, then you should use Z1.4. The API chemical test probably yields a numerical result for which you can calculate the average and standard deviation. Then, the proper standard to use is Z1.9. If the micro test gives you a numerical result, then you can use Z1.9 for it as well.

One thing to consider is the fact that the materials are from a
batch. If the batch can be assumed to be completely mixed without settling or separation prior to loading into final packaging, then the API chemical test may only need to be done on the batch, not on the final product. Micro testing, which can be affected by the cleanliness of the packaging equipment, probably needs to be done on the final product.

Brenda Bishop
U.S. Liaison to TC 69/WG3
ASQ CQE, CQA, CMQ/OE, CRE, SSBB, CQIA
Belleville, Illinois

For more on this topic, please visit ASQ’s website.

Z1.4:2008 Inspection Levels

Q: I am reading ANSI/ASQ Z1.4-2008: Sampling procedures and tables for inspection by attributes, and there is a small section regarding inspection level (clause 9.2). Can I get further explanation of how one would justify that less discrimination is needed?

For example, my lot size is 720 which means, under general inspection level II, the sample size would be 80 (code J). However, we run a variety of tests, including microbial and heavy metal testing. These tests are very costly. We would like to justify that we can abide by level I or even lower if possible. Do you have any advice?

The product is a liquid dietary supplement.

A: Justification of a specific inspection level is the responsibility of the “responsible party.” Rationale for using one of the special levels (S-1, S-2, S-3, S-4) could be based on the cost or time to perform a test. Less discrimination means that the actual Acceptable Quality Level (AQL) on the table underestimates the true AQL, as the sample size has been reduced from the table-suggested sample size (i.e. Table II-A has sample level G of 32 for a lot size of 151 to 280, while General Inspection level I would require Letter E or 13 samples for the same lot size).

Justification of a sampling plan is based on risk and a sampling plan can be justified based on the cost of the test, assuming you are willing to take larger sampling risks. If you use one of the special sampling plans based on the cost of the test, it is helpful to calculate the actual AQL and Limiting Quality (LQ) using the following formulas.

You solve the equation for AQL and LQ for a given sample size (n) and defects allowed (x):

Steven Walfish
Secretary, U.S. TAG to ISO/TC 69
ASQ CQE
Principal Statistician, BD
http://statisticaloutsourcingservices.com

For more on this topic, please visit ASQ’s website.