Guidance on Supplier Qualification - Phase 1 pharma manufacturing

[AwwPhooey]

Hello everyone - Thank you in advance for reading this post.

I've recently started a role within Supplier Quality at a clinical immunopharma company, working on developing the Supplier Management process. Was hoping to get some input from you experts on your experience with Supplier qualification requirements during (barely) Phase 1 operations (my SQ background is commercial). I've spoken with former colleagues and just purchased a copy of PDA Technical Report 56 (Application of Phase-Appropriate Quality System and cGMP to the Development of Therapeutic Protein Substance) for guidance.

Within that report, Section 4.0-1 (Quality System and cGMP Recommendations by Stage Development), there is a section called Materials, and then the requirements stipulated for each Phase 1-3. Phase 1 requirements are indicated as follows:

- Good Control over materials is required to ensure proper receipt, storage, release and integrity (No problem, straight forward, we have controls in place)

- The extent of supplier qualification depends both upon the phase of development and upon criticality of the material (Ok. I understand the point here, but the 'extent' is what I'm struggling to grasp).

- Material is classified through a risk-based approach, utilizing process knowledge as it becomes available from process development. In the QC area, critical reagents should be defined and included in the documentation. (My approach would be, meeting with SMEs from different areas ((e.g. Technology, MFG, QA, etc)) to come up with a categorization schema such as Material Type, Sub-Type, then a ranking system on impact to final product based on categories such as sterility, contact with final product, etc. This is somewhat what we did at my last company which was all commercial production. We had these systems in place for commercial, but sounds like this needs to be fully developed in Phase 1.)

- Vendors should be qualified utilizing a risk-based approach - qualifications should be more thorough (eg. Audits versus questionnaires) for higher risk materials that are critical to the process and product quality. (We have a risk matrix which factors Impact vs Likelihood- Impact being the impact of material issues on final product vs Likelihood- ability to receive quality material on a consistent basis. There is one issue with this approach for me, we measure Likelihood right out the gate with a new supplier before we have any history with that Supplier. We ascertain this based on their response from supplier questionnaires, then whatever data I find online regarding market recall, regulatory audit observations, reputation. But I digress here).

- Commercial suppliers are identified during later phases. The frequency of vendor reassessment should be determined using a risk-based approach. (Not quite sure what "commercial suppliers" means here. And why they use supplier here vs vendor elsewhere. Unless they are referring to 'Supplier' meaning 'Distributor'?)

- Inventory control should be managed to maintain integrity and prevent mixups and utilize FIFO or FEFO. (Not a problem, we already do this).

- Vendor C of A with an ID test can be used to accept incoming raw materials. (Not a problem, we already do this).

- Storage and expiration as per vendor recommendation. (Not a problem, we already do this).

- If possible, use of animal derived raw material should be avoided due to concerns about a adventitious agents if used additional certification of the safety of the origin material may be required. (Not a problem, we already do this).

For Phase 2 and Phase 3, it says "Same Controls as in Phases 1 and 2" and then that somewhat confusing statement from above "In addition, suppliers should be fully qualified during Phase 3 with risks to supplies identified and mitigated." There is also in addition, "It is highly recommended to have back-up suppliers, when possible" which is fine, we will evaluate need for secondary suppliers as we go.

So in short it seems that, basically, we need to have a completely developed Phase 3 ready supplier management program developed in Phase 1. Am I looking at this the right way?

I'd appreciate any advice you'd offer. Thanks in advance, everyone!

 

[Ed Panek]

Here are some thoughts...

• The extent of supplier qualification: As you noted, the extent of supplier qualification depends on the phase of development and criticality of the material. This means that for Phase 1, you may not need to conduct as thorough a qualification process as you would for later phases. However, you still need to have good control over materials and ensure proper receipt, storage, release, and integrity.
• Risk-based approach: The risk-based approach is crucial for supplier qualification at all stages of development. This means that you need to identify and classify materials based on their risk level and utilize process knowledge as it becomes available from process development. Your proposed approach of meeting with SMEs from different areas to come up with a categorization schema is a good starting point.
• Vendor qualification: Vendor qualification should be based on a risk-based approach, with more thorough qualifications for higher risk materials that are critical to the process and product quality. Your risk matrix that factors in Impact vs. Likelihood is a good way to assess the risk level of different suppliers. Keep in mind that while you may not have any history with a new supplier, you can still gather information from questionnaires, online data, and other sources to assess their likelihood of providing quality material.
• Commercial suppliers: The term "commercial suppliers" likely refers to suppliers that provide materials for commercial production. During Phase 1, you may not yet have identified all the suppliers that you will use for commercial production, so the focus is on establishing a supplier management program that can be scaled up as you move into later phases.
• Back-up suppliers: Having back-up suppliers is highly recommended for all phases of development. This is because unexpected supply chain disruptions can occur at any time, and having a back-up supplier can help minimize the impact on your operations.

For example, for feasibility you might want samples to demonstrate you can achieve a result close to desired. Perhaps you even demand optimal performance here. If not, can you tune your processing paramters given the quality of the raw materials? What can the supplier guarantee for all lots received? Is there an agreed to testing method prior to shipment to you? maybe only 25% of their material will work for you. How is that process defined?

As you get more confident you might enact certain control over process variables. You may request samples from different production lines, using different raw material lots, using different shipping methods. Is your process tied into the qualities available at only one supplier? Can it tolerate another supplier with no loss of specifications? If it cant, why not? Is the failure critical to the end product or not? What would the scrap rate be?

I worked a a film printer medical device company. We sourced raw film from AGFA in Belgium but because our printhead and imaging technology were ours and not AGFAs not all their film would work for us. We solved this by providing a printer of ours at the end of their film finishing line. They would take samples and try them in our printer. We p aid a premium for this requirement and because we were 15% of their total sales this was quickly agreed to.

 

[AwwPhooey]

Thank you for your input Ed.

 

[questionmark]

This is an excellent follow-up, Ed. I am also building a Supplier Quality process at a small, not yet phase 1 biotech company. The company is also trying to initiate a CSA approach to software simultaneously. Currently, my process assesses software providers, such as those supplying our QMS system; however, based on prior experience, I have defined that suppliers providing equipment or instruments are out of scope. Some equipment and instruments, however, have software components used to operate the equipment or instrument. Does anyone have any experience with this and share insights on the best phased approach? Should equipment and instrument vendors appear on an approved vendor list?

 

[derickson]

This is an excellent follow-up, Ed. I am also building a Supplier Quality process at a small, not yet phase 1 biotech company. The company is also trying to initiate a CSA approach to software simultaneously. Currently, my process assesses software providers, such as those supplying our QMS system; however, based on prior experience, I have defined that suppliers providing equipment or instruments are out of scope. Some equipment and instruments, however, have software components used to operate the equipment or instrument. Does anyone have any experience with this and share insights on the best phased approach? Should equipment and instrument vendors appear on an approved vendor list?

I have been researching online for the last couple hours trying to answer the same question, for the same reason. Since the CSA approach relies on the supplier evaluation process to confirm that developer of the software (in some cases the manufacturing equipment developer/manufacturer) has processes in place to ensure their SW quality, I now think we need to add the suppliers of manufacturing equipment that include SW (or even firmware) to our Approved Supplier list. But since I have not required them to be included them in the past, this will create a lot of extra work. Since the CSA process was intended to streamline the process, I am not sure my interpretation is correct. Have you made a decision since you posted this question a couple months ago?

Thanks for sharing!

 

[san777das]

I have been researching online for the last couple hours trying to answer the same question, for the same reason. Since the CSA approach relies on the supplier evaluation process to confirm that developer of the software (in some cases the manufacturing equipment developer/manufacturer) has processes in place to ensure their SW quality, I now think we need to add the suppliers of manufacturing equipment that include SW (or even firmware) to our Approved Supplier list. But since I have not required them to be included them in the past, this will create a lot of extra work. Since the CSA process was intended to streamline the process, I am not sure my interpretation is correct. Have you made a decision since you posted this question a couple months ago?

Thanks for sharing!

Whatt approach did you take for adding the software vendors on the ASL? Did you also audit any of the software vendors?

 

[RD RA]

Hi all,

Just following up are third-party regulatory agencies or consultancies required to be listed in the Approved Supplier List (ASL)? if yes, why?

I’d appreciate any input or clarification on this.