What MAH's Need to Know About Outsourcing

The continued growth of outsourcing of manufacturing in the pharmaceutical industry and the use of more complicated supply chains means that in certain situations the Marketing Authorisation Holder (MAH) can become very far removed from manufacturing process and products. However, it needs to be remembered that the MAH remains ultimately responsible for the safety, quality, and efficacy of the product over its lifetime. In this article, our pharmaceutical regulatory affairs team considers the problems that might arise and the measures that you can take to prevent them from arising.

Who Is The Marketing Authorisation Holder?

Firstly, the MAH is the company or legal entity in whose name the Marketing Authorisation has been granted. It should be noted that the way in which a MAH is expected to interact with the registered manufacturing sites in a specific marketing authorisation is not clearly laid out in specific guidance. Therefore, it is crucial that the MAH understands their role and responsibility in facilitating GMP compliance at all outsourced manufacturing sites. These roles and responsibilities include:

• The MAH should ensure that documented agreements and robust communication process are in place between the MAH and the contractor.
• The definition and management of the necessary documents and procedures must fall within the scope of their quality management system.

We often discover, in our early conversations with new client companies, that complex multi-tiered supply chains can confuse issues and this understanding can become unclear to the MAH or the Contract Manufacturing Organisation’s (CMO’s).

‘Delegate Activities, Not Responsibility’

It is very important for companies to understand that the MAH can ultimately delegate activities but not responsibility. Outsourcing of manufacturing and other activities is ever increasing across the pharmaceutical sector.  This has been driven, in part, by mergers and acquisitions.  However, as changes happen, we have found, in our experience, that issues get ‘missed’. To ensure that issues do not get forgotten, we always advise that there is a need to deepen working relationships with specific government and health agencies.  Outsourcing brings with it many benefits, such as improved processes and standards across the industry through the spread of knowledge and technology globally.   However, if the supply chain becomes too complicated the MAH oversight of processes can be reduced significantly. The lack of supply chain oversight means it can be more difficult to manage and assess the entire supply chain. This increases risks including quality non-compliances.

3 Quality Risks To Consider

In situations such as this, experience has taught us that there are 3 quality risks:

1. Data integrity issues at supplier plants
2. Issues with regulatory oversight and communication of regulatory updates across all sites.
3. Inadequate Quality agreements due to the lack of understanding of roles and responsibilities

In cases, where companies have been acquired, operations and resources can be reduced during the initial stages. This often leads to limited personnel availability to perform the day to day quality functions that are required to ensure compliant supply chain control and management.

9 Issues To Consider

We have considered the tasks that need to be completed, and below we are highlighting 9 issues that should be considered by companies acquiring/involved in a merger or similar:

1. Lack of supply chain gap analysis, leading to gaps in supply chain knowledge
2. Reduction in the frequency of supplier assessments
3. Insufficient resources available to properly manage quality issues
4. Poor management of materials e.g. cold chain and supplier GMP oversight
5. Inadequate communication and sharing of important quality information between MAH and suppliers
6. To improve MAH oversight of the entire supply chain:
7. Adequate resources and processes should be available to control all outsourced activities.
8. Regular on-site audits of all suppliers and contractors must be conducted
9. Regular review of all suppliers and appropriate records maintained

Conclusion

If embarking on a merger or if your company is acquiring another company, it is useful to remember the following points:

• Adequate supplier and quality agreements must be in place with all contractors.
• The agreements must clearly define the agreed roles and responsibilities of all parties.
• The agreement must also detail how information/Issues are communicated between parties to prevent any delays in the sharing of important information.
• To prevent problems in future operations it is vital that enough time and resources are spent on selecting affiliates and partners for outsourcing. The decision should be based on quality and not solely on the associated cost.
• When selecting companies to partner with on projects it is also useful to consider the ‘pain points’ that might arise.
• Language barriers often arise during a project as the issue has often not been considered in the evaluation of suppliers.  While this might sound like a simple mistake, it is quite common.  Our experience has shown us that early engagement between the key stakeholders involved in the project from the client side with the project personnel on the supplier side is critical to the success of the project.  Doing so enables both parties to better plan projects.
• MAH lack of understanding of the National Regulations in the ROW country and the affiliates lack of understanding of EU requirements.
• Can you or your regulatory partner build a trusting relationship with the company and agency.

There can be many differences in how the national regulatory authority operates in comparison to the EU and FDA and their specific regulatory requirements e.g. Legalisation of documents and the acceptance of paper only GMP documents.  You should ensure that you have factored this into your initial planning. Finally, the MAH should have a clear understanding of the requirements and if they can be adhered to before making the final decision to proceed with the global partner, this will lead to a smoother road ahead. We have significant experience of working on numerous projects of this type where the MAH has outsourced the processes and manufacturing to third parties.  If you would like to discuss your project with our team of experts, then please call us today on 00353 52 61 76706, email us:  info@acornregulatory.com or complete the details below. Also, if you would like to ask one of our regulatory experts a question relating to marketing authorisations, then please complete the webform below and place your question in the ‘How Can We Help You’ box. [ninja_form id=82]

Further Reading on MAH Responsibilities

Using a US Dossier for a European MA Application? Here Is What You Need To Know

Over the years, we have worked with a significant number of US innovator companies and supported them in getting their ‘US developed medicinal product’ registered as a medicinal product in Europe. In this article, we look at some of the issues we have encountered in taking a US developed dossier for a new marketing authorisation.  Read more here.

Type I Variation: Apparently Not So Simple

Regulatory professionals would generally perceive the Type I variation as a fairly simple regulatory procedure. New figures released by the EMA suggest differently. Statistical data released by the EMA has revealed that 44% of all Type I variation applications received for assessment by the EMA contain errors. It is reasonable to assume that these figures are mirrored for National Procedures and Mutually Recognised Procedure variations. The figure of 44% is quite high when you consider that the variations classification guideline for Type I variations is quite detailed. The pharmaceutical industry is always pursuing initiatives to achieve “perfection” in our processes. This lean approach increases efficiency, improves quality, and achieves what the Pharmaceutical industry is primarily focused on, providing safe and effective medicinal products to the public. The function of Regulatory Affairs is no different. Identifying areas of improvement and increasing “Right First Time” is a goal of all regulatory personnel. This article details the common deficiency areas with the idea of promoting awareness. Read more here.

Ten Questions To Ask When Moving from A DCP Close Out To Product Launch

When a Decentralised Procedure (DCP) or a Mutually Recognised Product (MRP) process is drawing to a close, much of the emphasis is placed on getting a “positive opinion”. However, it is at a time like this, when submitting the final sequences that the focus on what comes next often gets lost. Frequently, companies close out their regulatory procedures only to be ill-prepared for the national phases and the product launch. What preparatory work should be done upfront to avoid this?  We look at the issue and answer 10 of the most common questions relating to a DCP close-out.  We hope that they will be useful to you in moving to a product launch. Read the full article here.