Good Distribution Practice - Auditing

‘Quality’ has become a more embracing and holistic notion concerning itself not only with the distribution of pharmaceutical products but also with those processes that may impact on the distribution process itself.

As the pharmaceutical industry has evolved, quality is not only concerned with the safety and efficacy of medicinal products but also the continual improvement of the processes involved in pharmaceutical distribution.

In order to ensure continual improvement, performing and reviewing feedback from different types of audits are vital in ensuring that quality is maintained in an organisations quality management system (QMS) and will allow for the development of some crucial processes within it such as Deviation and CAPA Management, Quality Risk Management, Management Review, Self Inspection processes and more. In addition, critical evaluation through audits will ensure that an organisations operations conform to established standards.

ISO 19011 suggests the following:

The principles of auditing: “make the audit an effective and reliable tool in support of management policies and controls, by providing information on which an organisation can act to improve its performance”.

Identification of “opportunities for potential improvement”.

In the pharmaceutical industry, the primary purpose of an audit is to assess the effectiveness of an organisations’ QMS system and its adherence to established standards, regulations and best practices. The following examples are where an audit is required which include:

• To look for compliance
• For-cause audit (following a deviation)
• Identifying risks
• Supplier audit and evaluation
• Following a change
• To promote improvements
• Regulatory Requirement

Quality audits come in different forms, each with a different scope. The three different types of audits in the pharmaceutical industry which include 1st, 2nd and 3rd party audits

First Party Audits – Internal auditsg. “Self-Inspections”

As per GDP guidelines, Self-Inspections should be conducted periodically and form an integral part of organisations self-assessment and improvement efforts. They provide an internal perspective on quality and compliance.

• To verify the implementation and effectiveness of the quality management system
• To identify problems and risks in organisational processes
• To evaluate corrective actions
• To promote continual improvement

Second Party Audits – External audits g. “Supplier and Third-Party Provider audits”.

Second party audits are crucial for organisations that rely on external suppliers which will ensure quality and compliance is maintained throughout the supply chain.

• A risk-based approach to evaluate suppliers and third-party providers
• Opportunity to follow up on areas of potential concern from a previous audit
• After a change
• After a deficiency

Third Party Audits – External auditsg. “Regulatory or Accreditation Inspections” i.e. MHRA, ISO.

A third-party audit is an independent examination conducted by an external auditor and has no affiliations with the organisation being audited. They are often essential for obtaining certifications and demonstrating compliance to regulatory authorities.

 

• Legal requirement of GDP
• For certification, accreditation or regulatory purposes
• Risk based
• Re-inspection of a site
• Following a change, new site, new RP

A quality audit is a structured and systematic approach which will generally consist of key phases such as: PLANNING, ASSESMENT, REPORT & FOLLOW-UP.

1. P – Planning

• Identify scope and objectives of the audit – why are we auditing, which areas are we planning to look at? - i.e. warehouse, computer systems, goods in.
• Request documentation (Some assessment can be done at the planning stage by requesting documentation before-hand i.e. organograms, company policies, quality manual, certain procedures etc)
• Appoint a lead auditor if there is a team of auditors
• Establish the criteria and standards against which the audit will be conducted i.e. HMR 2012 regulations, GDP guidelines.
• Develop a timeline and schedule for the audit activities to be conducted
• Start planning an audit agenda for the day

2. A – Assessment

• Following an initial opening meeting, the audit assessment will begin to take place
• Observation of processes and activities to assess the organisations’ compliance with established standards.
• Documentation review (of which some can be done at the planning stage) to assess the organisations processes.
• Engaging with key personnel to gather information about the audited areas
• Closing meeting with the auditees.

3. R – Report

• After completing the audit activities, a detailed report is generated by the auditor(s) and communicated to the auditee which will document the findings of the audited areas and allow for the auditee(s) to make informed decisions regarding any improvements.
• The report is submitted within a pre-agreed timeframe with the auditee(s).

4. F – Follow-up

• The final phase is the collaboration of the auditors and auditees to ensure that corrective actions of any findings are implemented in addressing any identified issues.
• The auditees will address any non-conformities and areas for improvement and the auditor may request verification to ensure that the corrective actions have been effectively implemented.
• The organisation will use the audit findings to drive ongoing improvement and enhance its quality management system.

Overall, the follow-up phase will have a lasting impact on the organisation’s quality and compliance efforts.

• Verifying the organisations quality policy and objectives
• Reviewing documents as part of the QMS to ensure that they are maintained and up to date with current legislations and current company activities
• Reviewing records and logs to ensure accurate documentation of processes and wholesaling activities
• Evaluating and assessing key processes
• Verifying adherence to established standards, regulations and legal requirements
• Ensuring that all necessary certifications and licences are valid and current
• Reviewing the organisation’s risk assessment and mitigation strategies and ensuring plans are in place for identified risks
• Confirm the existence and implementation of deviation management and corrective action procedures and their effectiveness
• Verifying that personnel are adequately trained on GDP and skilled for their respective roles
• Evaluating the effectiveness of training programmes
• Visiting storage areas and analysing the goods in and out process
• Ensuring that safety, quality and efficiency is maintained throughout the organisation.

The MHRA carry out inspections to ensure that distribution sites comply to GDP guidelines. In addition, the MHRA will conduct inspections on organisations based on the following:

• New applications for WDA(H) Licence
• Following variation submission to changes of a current WDA(H) licence i.e. change of premises or key personnel such as the RP
• Risk-based inspections – which can be conducted periodically based on the company’s risk score
• Triggered inspections due to possible GDP breaches – *The inspector can send little or no notification of these inspections*

You will usually receive a notification of an upcoming GDP Inspection which will either be conducted on-site or remotely and an inspection plan which will detail the will be provided in advance by the inspectorate.

Guidance: https://www.gov.uk/guidance/good-manufacturing-practice-and-good-distribution-practice#types-of-inspection

Based on the findings of the inspection, the Inspectorate will grade their findings based on the following gradings which will sent in an response to the Licence Holder(s) of the WDA(H) Holder:

1. Critical

• A deficiency which has produced or significantly risks producing a product which is harmful to humans or veterinary patients or which could result in a harmful residue in a food-producing animal.
• Any departure from good distribution practice that results in a significant risk to patients. This includes an activity which increases the risk of counterfeit medicines reaching patients.

2. Major

A non-critical deficiency which:

• has or may produce a product that doesn’t comply with its marketing authorisation
• indicates a major deviation from GDP or from the terms of the wholesale licence
• indicates a failure of the Responsible Person to fulfil their legal duties
• a combination of several ‘other’ deficiencies which on their own may not be major but together may represent a major deficiency and should be explained and reported as such

3. Other

• A deficiency which cannot be classified as either critical or major or there is not enough information to classify it as critical or major but which indicates a departure from good manufacturing and distribution practice.

During inspection, transparency and openness is vital to building trust between the organisation and the inspector. If you know there’s a gap, be open about it.

Never try to “hide the problem” or “dig/talk your way out of it” as the inspectors are far too shrewd and rarely does this approach result in a positive outcome. If the inspector gets the impression that you’re not being entirely truthful or open, they are more likely to keep digging and any trust built will be eroded.