The implementation of a robust Quality Management System (QMS) is a key success factor for clinical development with the goal of reaching marketing authorization. As important as your QMS is during your product development phase, it’s equally important during your commercialization phase and through the product lifecycle. However, your quality work will change between the two phases depending on the type of company you are. In this blog, we explain the difference and provide an overview of the steps and the skills required for both phases so you can effectively bring your products to market.
Switching from a Clinical to Commercial Mindset
First, we provide an overview of the differences in quality work, and therefore the requirements of your QMS between the Clinical and Commercial phase.
Pre-Approval
- During the development phase, the most important part of your quality work revolves around gathering data to support your application and the development of your product. This includes sponsor oversight of your CROs and your clinical studies → Good Clinical Practice (GCP).
- From a Good Manufacturing Practice (GMP) perspective, the QMS needs to focus on your product development including oversight of CDMOs, formulation development, IMPDs, validation batches, stability and blinding of your clinical trials.
Post-Approval
- A post-approval QMS focuses on the processes to assure that your product is manufactured (GMP) and distributed (GDP) according to what you have concluded during your product development. This is what you have submitted during your MA-application. This also includes lifecycle management as changes in CMO and continued product development appear.
As a MAH, you have the overall accountability for the quality of the product, even if your supply chain is fully outsourced. This is established in the Annex 16 of EudraLex Vol 4 that defines GMP-activities in EU:
The ultimate responsibility for the performance of a medicinal product over its lifetime, its safety, quality and efficacy, lies with the marketing authorization holder (MAH).
On top of that, the EMA has also written a concept paper defining in the legislation where MAHs have an extended responsibility:
So, between the responsibilities you have, and the diverse requirements needed for different aspects of commercialization, what exactly are the questions you need to ask yourself to prepare? We have created an overview:
Preparations Before Your MA (GMP)
- In advance of your MA, you need to make sure your supply chain is prepared for commercial supply
- Drug substance (DS)
- API-manufacturing
- Is the site in EU or is importation required?
- Has the site acquired applicable EU GMP certification from EU competent authority?
- Have you qualified the site, including audit?
- Do you have a technical agreement in place defining roles and responsibilities?
- Drug product (DP)
- CMOs for formulation, packaging, and release
- Is the manufacturing done in EU or outside?
- Import release in EU is required for partially or fully manufactured products outside EU. Extra QC in EU might be required depending on what country the product is imported from.
- Does the CMO site have manufacturing license for the type of activity/formulation you are requesting?
- Successful tech transfer from your development site?
- Validation batches and stability data from the CMO to support your MAA?
- Have you qualified the site including audit?
- Do you have a technical agreement in place defining roles and responsibilities?
- Validated transportation routes between the different CMOs, if multiple are used?
- Capability for serialization?
Preparations Before Your MA (GDP)
- For distributing your product, you need to source a 3PL for warehousing and transport
- Are your 3PL experienced in pharma?
- Does it have the correct licenses, i.e. WDA and controlled substances?
- Transport’s temperature controlled and monitored?
- Is transport validation required or is a risk assessment enough?
- Auditing of warehouses and transportation firms
- Qualification of buyers
- Service agreement and/or technical agreement
- Wholesale dealer authorization (WDA). To be able to sell your product in EU, you need to have a WDA, even if the supply chain Is fully outsourced. Wholesale includes:
- Procuring
- Holding
- Supplying or exporting medicinal products apart from supplying medicinal products to the public
- Read more about WDA in my previous blog post about Understanding Responsible Person and Wholesaler Dealers Authorization
How ProPharma Can Support You
To prepare for your commercialization, ProPharma’s experienced consulting team will support and guide you with all the different aspects of GxP-environments. This includes:
- Auditing
- QMS-development and eQMS-system
- Product release though ProPharma MIA-license
- MIA application and QP-services
- WDA application and RP-services
- CMO-selection
- Tech Transfer
- Stability and validation support
- Nitrosamine risk assessments
- Computerized system validation
- Data Integrity
- Commissioning and qualification
If you want to discuss your specific case with an expert, please contact us.
