4 Posts
All,
This is my very first post so I apologize in advance if this is not the correct forum for this type of question. I've recently taken over our Incoming Quality group and I'm looking to do some streamlining and process improvements in the area. What I'm wondering is if there are any pharma companies out there that have successfully implemented programs in which they have leveraged supplier quality to drastically reduce sampling and inspection especially when receiving multiple shipments of one vendor lot of a component. I know that CFR requires that at least an identification needs to be performed on the components received for each lot of each shipment but I was curious if anyone has implemented a very minimal approach that is "passing" FDA and other regulatory agency muster.
I brought this question to the Standards community but it was suggested that I might get more feedback here :)
Thanks in advance,
K. Anderson
This is my very first post so I apologize in advance if this is not the correct forum for this type of question. I've recently taken over our Incoming Quality group and I'm looking to do some streamlining and process improvements in the area. What I'm wondering is if there are any pharma companies out there that have successfully implemented programs in which they have leveraged supplier quality to drastically reduce sampling and inspection especially when receiving multiple shipments of one vendor lot of a component. I know that CFR requires that at least an identification needs to be performed on the components received for each lot of each shipment but I was curious if anyone has implemented a very minimal approach that is "passing" FDA and other regulatory agency muster.
I brought this question to the Standards community but it was suggested that I might get more feedback here :)
Thanks in advance,
K. Anderson
6 Replies
196 Posts
Okay, I think it is important to have established a rigorous supplier management program, here's a flowchart to start some benchmarking. This approach was one used at a site under consent decree I was at for 6 years, and trust me it passed a lot of FDA and other regulatory agency scrutiny.
The establishment of categories is fairly critical.
Your table will look different, depending on what type of pharma you do, but probably not radically different. I'm in biologics, and it's been a decade since I've done much small molecule. But I'd guess this table is fairly easy to figure out.
First you qualify the supplier. This establishes they meet the criteria in the table above.
Once qualified, there is a pathway for certification. Certification will enable materials to be dispositioned with reduced in-coming testing and is based on documented supplier performance history (including material consistency) and risk assessment.
To be eligible for certification, the following criteria apply:
Following supplier and material certification, full testing must be performed on at least one lot received annually and test results must meet the criteria in the approved specification document. Reduced testing for other lots includes at a minimum, material identity testing (confirmatory testing), and a review of the supplier’s COA results and other supplier documentation as listed in the corresponding material specification document.
Certified status must be removed when any of the following events occur, unless a risk assessment is performed to justify not removing the qualified status for one or more materials provided by the supplier:
Love other folks thoughts on how they do this.
The establishment of categories is fairly critical.
| Category | Definition | Material | Material Onboarding/Qualification Requirements |
| 1 | Materials, printed materials or services whose failure is likely to impact product quality | Animal derived/biologic material used in product manufacture Critical (Key) Raw Materials Custom materials such as containers, closures, or cell culture media powders/blends used in product manufacturing APIs Final sterilization filters Finished product primary packaging materials (container/closure) Printed materials / labelling (secondary packaging materials) Raw materials that are part of the finished product Materials received from certified suppliers |
Material specification Part number Site audit User requirements/fit for use for materials Quality agreement Material qualification testing Business Assessment |
| 2 | Materials or services whose failure may impact product quality | Production raw materials/ingredients (e.g. salts and media components) Materials that are not Category 1 but are listed in the drug filings Manufacturing processing consumables and components (e.g. standards, tubing assemblies, filters, chromatography media, filters) All production raw materials that are required to be sterile All production components that are required to be sterile or have product contact, including single-use / disposable materials Biological indicators for sterilization processes Computer systems/software used to control GMP manufacturing and testing Cleaning materials that have process contact Disinfectants used in production-controlled areas HEPA filters used in aseptic processing Diaphragms, gaskets and o-rings that are product contract |
Material specification Part number Site audit or supplier questionnaire as determined by Quality User requirements/fit for use for materials Minimum Quality Requirements agreement applicable to type of material Material qualification testing as prescribed by applicable fit-for-use Certificate for polymeric product contact parts Business assessment NOTES: Computer system/software does not require material specification or part number |
| 3 | Materials whose failure would not directly impair product safety or functionality or they have no direct contact with the product | Cold chain shipper containers Non-sterile GMP testing/cleaning supplies with no process contact Packaging items that are not considered primary or secondary packaging materials |
Supplier questionnaire Material Master number User requirements Business Assessment |
| 4 | Materials used exclusively for development | Reagents and analytical standards used exclusively in laboratory areas for development purposes only |
Material Master number |
Your table will look different, depending on what type of pharma you do, but probably not radically different. I'm in biologics, and it's been a decade since I've done much small molecule. But I'd guess this table is fairly easy to figure out.
First you qualify the supplier. This establishes they meet the criteria in the table above.
Once qualified, there is a pathway for certification. Certification will enable materials to be dispositioned with reduced in-coming testing and is based on documented supplier performance history (including material consistency) and risk assessment.
To be eligible for certification, the following criteria apply:
-
-
- a history of satisfactory supplier performance
- evaluation of consecutive test data from a minimum of 3 distinct lots of material received
- a reliable and consistent quality and compliance history as evidenced through audits and evaluations
-
Following supplier and material certification, full testing must be performed on at least one lot received annually and test results must meet the criteria in the approved specification document. Reduced testing for other lots includes at a minimum, material identity testing (confirmatory testing), and a review of the supplier’s COA results and other supplier documentation as listed in the corresponding material specification document.
Certified status must be removed when any of the following events occur, unless a risk assessment is performed to justify not removing the qualified status for one or more materials provided by the supplier:
-
-
- a non-conformance is identified on any parameter listed in the COA
- critical or major audit observations related to the supplier’s sampling, quality control or release activities
- a deficiency in the supplier’s quality system was identified during routine monitoring (e.g. a manufacturing change not reported)
-
Love other folks thoughts on how they do this.
4 Posts
Jeremiah -
This is fabulous and is similar to what we're doing currently so that's reassuring. Thanks so much. Might I ask what was considered full vs reduced sampling? And also whether there was any justification for using a minimum of 3 lots vs any other number of lots (since I know ANSI standard has normal to reduced sampling based on 10 lots)?
Thanks again!
Krista
This is fabulous and is similar to what we're doing currently so that's reassuring. Thanks so much. Might I ask what was considered full vs reduced sampling? And also whether there was any justification for using a minimum of 3 lots vs any other number of lots (since I know ANSI standard has normal to reduced sampling based on 10 lots)?
Thanks again!
Krista
196 Posts
Might I ask what was considered full vs reduced sampling? And also whether there was any justification for using a minimum of 3 lots vs any other number of lots (since I know ANSI standard has normal to reduced sampling based on 10 lots)?
We follow ANSI/ASQ Z-1.4 for for determining sampling amounts. I don't remember where 3 lots came from, my guess is pharma quality superstition and laziness but I will check around and see if anyone has a better justification.
20 Posts
This may or may not directly relate to the thread, but thought this would shed some valuable light on Incoming Quality/Supplier Quality, etc
https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/cosmelab-co-ltd-590480-01092020
https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/cosmelab-co-ltd-590480-01092020
196 Posts
The Cosmelab Warning Letter is a great example of why this is so important.
A recent, last half of 2019, 483 that should be discussed and considered as one moves with decreasing testing is:
These two (a month apart, there is a story there I am sure) go to the heart of why it is important to have a qualification program and a documented approach for when you reduce testing.
A recent, last half of 2019, 483 that should be discussed and considered as one moves with decreasing testing is:
| EyePoint Pharmaceuticals, Watertown | United States | Human Drugs | 08/28/2019 | OBSERVATION 9 Reports of analysis from component suppliers are accepted in lieu of testing each component for conformity with all appropriate written specifications, without establishing the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals. Specifically, The firm purchases purified water from a supplier to supplement the water from the firm's purified water system. The form has not qualified the supplier and the firm only relies upon the supplier's certificate of analysis. The firm has received approximately nine lots of purified water since February of 2019. |
| EyePoint Pharmaceuticals, Watertown | United States | Human Drugs | 08/28/2019 | OBSERVATION 9 Reports of analysis from component suppliers are accepted in lieu of testing each component for conformity with all appropriate written specifications, without establishing the reliability of the supplier's analyses through appropriate validation of the supplier's test results at appropriate intervals. Specifically, The firm purchases purified water from a supplier to supplement the water from the firm's purified water system. The form has not qualified the supplier and the firm only relies upon the supplier's certificate of analysis. The firm has received approximately nine lots of purified water since February of 2019. |
These two (a month apart, there is a story there I am sure) go to the heart of why it is important to have a qualification program and a documented approach for when you reduce testing.
