Any starting material intended for use in the production of medicinal products must be tested for identity, purity and quality. All deliveries of each batch of material must be sampled, tested and the results evaluated prior to manufacturing.
As the identity, purity and quality of a complete batch of material is concluded from a small fraction of the batch, sampling is an important operation. Negotiating the dilemma of how much to take, how many containers and the number of samples that may be blended to form a composite sample, while assuring that samples taken are representative of the whole batch relies on sound statistical and validation practices.
Benefits of testing starting materials:
- Patient safety
- To prevent costly manufacturing problems
- Comply with Marketing Authorisation (MA) / Drug Master File (DMF)
Depending on the supply chain and the extent of Supplier Qualification that has been carried out, each batch of starting material will either be fully tested, or a reduced testing program will be established. There are pros and cons to both.
The raw material specification (RMS) will include the validated test methods required to confirm the identity, purity and quality of the material. These test methods can be in-house methods specifically developed for the material or published pharmacopoeia methods (United States Pharmacopoeia, USP, European Pharmacopoeia, Ph.Eur, British Pharmacopoeia, BP, Japanese Pharmacopoeia, JP, or lesser known publications). When it comes to pharmaceuticals ‘generic’ does not mean identical. Any analytical method for a given product must be scientifically valid for its intended use.
Requirements for Sampling starting materials:
- Avoid contamination
- Representative sample(s)
- Assure identity of product in each raw material container
The raw material testing laboratory is a specialised laboratory with requirements for a wide range of equipment and analytical chemistry expertise. Raw material tests are “different & difficult” compared to the more routine nature of testing formulated product. There is a strong reliance on extensive wet chemical tests, particularly in pharmacopoeia monographs. Not all pharmacopoeias are harmonised or have harmonised test methods. Where product is destined to be supplied to multiple markets testing costs and times are often increased by testing to multiple monographs. Pharmacopoeia monographs are a minimum and general specification.
Other specific tests may need to be considered that are relevant to a specific formulation. These may be critical to demonstrate suitability and consistency of material quality, e.g functional tests. In addition to expensive equipment and experienced analytical personnel, raw material testing is not without challenges and Out of Specification results (OOS) can be commonplace.
Challenges testing starting materials:
- Compendial methods not robust enough
- Suppliers of raw materials don’t supply pharma only markets
- Supplier test methods used to generate batch Certificate of Analysis (CofA) not same as pharmacopoeia or MA, making comparison difficult
- Suppliers use non-compendial methods and validation status not available
For many routine QC laboratories RM testing is not within their experience. For efficiency and to allow the laboratory to focus on its core competencies (why purchase, qualify and maintain a £100K piece of equipment that may only be used a few times a year?) many manufacturers choose to outsource some or all of their raw material testing.
Specialist contract laboratories will perform tests multiple times a week, making them knowledgeable about the equipment and the test. Every manufacturers priority is to get product to market quickly and safely, letting a third-party specialist take care of raw material testing can very often achieve this. The decision to contract a laboratory partner begins with identifying the company needs and matching this to the contract laboratories capabilities. It’s worth noting that not all contract laboratories are equal.
There are often hidden value-added benefits that separate one laboratory from another and will usually explain why one laboratory is charging higher prices for what might appear to be the same service.
Benefits of using Contract Laboratory:
- Reduced equipment costs (underutilisation & qualification)
- Third party laboratories are unbiased
When you have chosen a contract laboratory that understands your priorities and requirements the relationship will work best if product information, specifications and details of sampling and transport are shared.
By working collaboratively with your contract laboratory, you will be rewarded with a quality partner taking care of QC compliance, giving you a “heads-up” and working with you if a quality problem arises.
Remember that raw material testing is not subject to the same regulatory restrictions that apply to final drug products. Contract laboratories only need to be named on a Manufacturing Authorisation if they are performing an ‘inspectable activity’ (Reference MHRA). These are:
- Microbiology, biological, chemical/physical testing of finished medicinal products
- Stability testing of finished marketed medicinal products
- Environmental Monitoring (EM) and/or process simulation work for sterile product manufacture
- Biological testing, if it needs to be done in accordance with cGMP (Annex 2 of EUGMP)
Contract laboratories that perform raw material, Active Pharmaceutical Ingredient (API) testing or produce research data for products that are not intended to be released onto the market or used in clinical trials do not need to be named on MA.
This means whatever ‘Brexit’ turns out to be raw material testing will carry on as it does today. Whether you send RM samples to the UK, EU or rest of the world you can continue to do so and continue the long-term relationship with your laboratory partner.
FDAS is a well-established, highly experienced independent testing laboratory that offers a comprehensive range of raw material tests. Founded by experts from within pharmaceutical manufacturing and working only to cGMP we understand the requirements of a modern, busy pharmaceutical manufacturer. Chose FDAS as your contract partner and we will help you get your products to market quickly and safely.
Please contact us to discuss any of your raw material testing requirements.
Technical Director, FDAS
+44 (0)115 912 4265
Tentamus UK Business Manager
+44 (0)7738 185654