Choosing a contract manufacturer usually commits you for many years, because switching later costs time, a new transfer and, for an authorised product, usually a variation to the marketing authorisation. It is therefore worth approaching the selection in a structured way. The following seven steps have proven useful, regardless of whether the product is a solid dosage form, a sterile product or packaging.
1. Define your requirements
Before you approach the first provider, you should clarify internally what you actually need. This includes the dosage form and the technology required, the expected volumes today and in a few years, the batch size, special requirements of the active substance such as high potency or sensitivity to light and moisture, and the markets for which the product is manufactured. It is also important whether the manufacturer should only produce, or also test, package and have the batches certified by its Qualified Person.
Record these requirements in writing and distinguish between must-have criteria and nice-to-haves. This makes the later steps much easier, because you can measure providers against a common list rather than against the impression left by a single conversation.
2. Draw up a long list
In the second step you collect potential providers, initially without filtering too strictly. Sources include directories such as this one, trade fairs, recommendations from your network and advice from consultants. Check early whether the provider holds a suitable manufacturing authorisation. In Germany it is granted under § 16 of the German Medicines Act (Arzneimittelgesetz, AMG) for a specific site and for specific medicinal products and dosage forms. Manufacturing authorisations and GMP certificates of manufacturers in the European Economic Area can be looked up in the European Medicines Agency’s publicly accessible EudraGMDP database, as can recorded cases of non-compliance with Good Manufacturing Practice. Using your must-have criteria, you then narrow the long list down to a shorter list of the companies you will actually contact.
3. Request with questionnaire
The first request contains a description of your project, as far as this is possible without confidential details, and a questionnaire. A standard questionnaire has the advantage that you can put the answers side by side. Also pay attention to how quickly and how carefully the provider replies. A provider that is hard to reach even at this stage will rarely do better once the project is running.
4. Confidentiality agreement
As soon as you share formulation, manufacturing process, specifications or analytical methods, a confidentiality agreement should be signed. Many providers have their own templates for this. Nevertheless, check which information is covered, how long confidentiality applies, whether the provider may pass the information on to subcontractors and what happens to the documents at the end. Only on this basis can the provider assess your project precisely enough to make a reliable quotation.
5. Audit
Chapter 7 of the EU GMP Guide requires you to verify, before outsourcing, that the contract acceptor is legally authorised, suitable and competent to carry out the work successfully. The usual means of doing so is an audit, performed either by you or by a contracted auditor. In the audit you look at the quality system, the premises and equipment, the documentation, the handling of deviations and changes, and the qualifications of the staff. For sterile products, questions on cleanroom technology and aseptic manufacturing are added.
An audit is not only a check but also the best opportunity to get to know the people you will later work with. How openly questions are answered and how findings are dealt with says a lot about the future collaboration. Record the result in a report and agree a deadline for remedying any deficiencies.
6. Quotation and quality agreement
In parallel with the audit or afterwards, you obtain binding quotations. When comparing them, look not only at the price per batch but also at the costs for transfer, validation batches, stability samples, minimum quantities, storage and the arrangements for rejected batches.
In addition to the commercial contract, you need a quality agreement. Chapter 7 of the EU GMP Guide and § 9 AMWHV require a written contract between contract giver and contract acceptor that clearly defines the duties of both parties. Under Chapter 7, the contract giver bears ultimate responsibility for ensuring that the outsourced activities are controlled, and continuously monitors the contract acceptor’s performance. In Germany this document is often called a Verantwortungsabgrenzung, a delimitation of responsibilities.
7. Technology transfer
The real work begins once the contract is signed. During technology transfer you hand over to the manufacturer everything it needs to manufacture and test your product reproducibly: formulation, manufacturing instructions, specifications, analytical methods and the experience gained during development. Chapter 7 explicitly obliges the contract giver to provide the contract acceptor with all the information and knowledge required for this. The manufacturer adapts the process to its equipment, the analytical methods are transferred, and validation batches show that the result meets your requirements.
For the transfer, plan a joint project plan with clear contact persons on both sides. It is precisely in this phase that you see whether the selection was a good one, because a manufacturer that talks openly about difficulties is worth more during the transfer than one that declares everything to be simple.
Finding suitable providers
You can find contract manufacturers in our directory under Contract manufacturing of solid dosage forms, Contract manufacturing of sterile medicinal products and Filling and packaging. For assessing potential partners before signing a contract, the providers of GMP audits can help you.