Lessons Learned from Continued GDP Inspections in the Netherlands Based on the New EU GDP Guidelines

• Dutch Healthcare Inspectorate
• Eli Lilly and Company

Introduction

The new EU GDP Guidelines was published on March 7, 2013 with an implementation period of six months until September 8, 2013. A new version of the Guidelines was published on 23rd November, 2013 for corrections of text and translation errors.¹ More guidance was included for quality management issues, responsible person, procurement/ storage, qualification/validation, temperature control including ambient condition, and computerised systems.

The general process of GDP inspections has a focus on quality. Some of the items to consider include but are not limited to frequency of GDP inspections, risk based planning, the topics to be inspected, is it an announced or unannounced inspection, the length of the inspection and the number of inspectors.

GDP Inspection Process

Usually the inspection is announced by a letter that may include the request of documents such as Site Master File (SMF) if available, index of the Quality Manual, and a list of products. The auditee confirms the receipt of the letter and prepares the requested documents.

The physical inspection begins with an introduction where the actual situation of the company is discussed and, for instance, the organization chart, including the responsible person (RP), is reviewed. A follow-up on the last inspection to check on the developments and changes made is conducted. A tour through the facilities is made and several quality registrations and pertinent documents are inspected. At the end of an inspection the findings are communicated during a closure meeting.

An inspection may result in three types of observations: critical (significant departure from GDP/risk for the patient), major (which indicates a (system) failure to carry out satisfactory procedures or a combination of several “other” deficiencies), or minor (a deficiency, which cannot be classified as either critical or major, but which indicates a departure from GDP) deficiencies which will be documented in the Inspection report. A reply from the audited organization with planned/ performed corrections is expected in a timely manner. The inspector(s) will ensure the proper action to correct the remarks and the inspection will be closed. After a positive inspection result a GDP certificate is issued by the health authorities.

In this publication we will present the inspection process and results of the continued GDP inspections through 2016 at companies with a wholesale license based on the new Guidelines. These represent 35 inspections at wholesalers with full assortment, parallel wholesalers, logistic providers with warehousing, pharmaceutical wholesalers/exporters, and manufacturers with wholesale activities. The results of inspections in early 2014 were reported by Bruinink and Bishara.²

Inspection Categories

• Management review - Chapter 1: A management review should be made based on analyses of the Quality registrations, discussion with the management and proposed improvements. It follows a plan-do-check-act process.
• Risk analysis - Chapter 1: Procedure and analysis of most important risks, planned measures to reduce risks. It may follow an identify, asses, treat/avoid, monitor/review process.
• Personnel, training, Responsible Person - Chapter 2: System for planning and registration of GDP training for all involved personnel, training based on new GDP Guidelines and job description for the Responsible Person.
• Temperature management in storage areas - Chapter 3: Monitoring, registration and control of temperature in storage area; alarm and follow-up; mapping of facility during summer and winter.
• Qualification of suppliers - Chapter 5: Based on authorization and other items such as a questionnaire about quality status; SOP should be in place.
• Returned goods - Chapter 6: System for handling and judging returned goods based on the criteria of the new GDP Guidelines, and availability of SOP.
• Self-inspections - Chapter 8: Should be planned, performed and reported periodically. There should be a follow-up on the findings and remarks. The SOP should be available.
• Transportation - Chapter 9: Audits should be performed and contracts (QA,TA) should be available, temperature is controlled based on a risk assessment.

Results

The results of the 35 inspections in 2016 showed 56 major findings. These are in the areas of temperature management in storage areas (12): temperature mapping and follow-up on alarms, lack of temperature control; quality management issues (10): risk management (6), management review (3), SOP’s/CAPA’s (3); transportation issues (10): qualification and lack of temperature control; Responsible Person (7); qualification of suppliers and customers (5). Table 1 shows the findings of the inspections and some of their remarks.

Table 1. Inspection results

The results of the 2016 inspections show improvements over the inspections in 2014. Areas for further improvements include management review: analysis of information, handling returned goods documentation and following the new criteria of the GDP Guidelines, qualification of suppliers based on quality information, temperature mapping and control in storage areas, follow–up on alarms, temperature excursions, self-inspections, temperature control of transportation, and performing tasks by the responsible person.

The report of Medicines & Healthcare products Regulatory Agency (MHRA) GDP Inspection Deficiency Data for 2016 published in November 2017 indicated that Quality system problems remain the most commonly observed issues.³ Top cited major GDP deficiency groups were 1.2 Quality Systems, 9.2 Transportation, 2.2 Responsible person, 5.2 Supplier Qualification, 3.3 Equipment, 4.2 Documentation, 3.2.1 Temperature Control, 5.5 Storage, and 5.3 Customer Qualification.

Note: A summary of the GDP inspection results was presented at PDA Pharmaceutical Cold & Supply Chain Logistics Conference, 10 - 11 October 2017, Prague, Czech Republic.

References

1. EU Guidelines on good distribution practice (GDP) of medicinal products for human use . European Commission, 23 November 2013 (2013/C 343/01.
2. Bruinink, R., and Bishara, R. H.: Lessons Learned from the First GDP Inspections in the Netherlands Based on the New EU GDP Guidelines. Journal Pharmaceutical Outsourcing, Volume 16, Issue 3, May / June 2015, pp. 34 – 36.
3. Brown, P., Madigan, T., and Ault M.: MHRA GDP Inspection Deficiency Data 2016. Published November 2017, https://www.gov.uk/government/uploads/ system/uploads/attachment data/file/667494/GDP 2016 Deficiency data.pdf.