Nature of non-compliance : In total 35 observations were made by the inspection team
over the course of the inspection. Five of them were categorised as major
deficiencies and therefore potentially leading to a risk to the human and
veterinary patient when using active pharmaceutical ingredients manufactured at
the inspected site. - The installation and execution of an Enterprise Resource
Planning System, hosting GMP relevant data but outside of the quality
management system, demonstrated a lack of QA oversight. - Repackaging operations
were conducted without any documentation and QA approval. - The issuance of
labels for raw materials and APIs was found inadequately controlled. - Within
the instrumental laboratory the Company violated basic principles on data
integrity, i.e. manual integration without justification and QA oversight. -
The Company’s approach on the validation of computerised systems (Shimadzu
LabSolutions) was considered as not in compliance with the requirements.
Action taken/proposed by the NCA :
Recall of batches already released
No immediate recall is needed. Each involved NCA should evaluate, following
assessment conducted in conjunction with MAHs, if a potential recall of
medicinal product is needed. The risk based evaluation should take in account
if there are alternative suppliers and potential risk of shortage. Given the
nature of non-compliances, assessment should include a complete retest of all
imported batches of active substance.
Prohibition of supply
Due to the nature of non-compliances, prohibition of supply is recommended.
Suspension or voiding of CEP (action to be taken by EDQM)
This inspection was carried out as part of the EDQM inspection Programm. The
impact of this NCS on the CEPs is to be decided by the EDQM. The concerned CEPs
are Simvastatin Butylated Hydroxy Anisole 50 - 150 ppm R1-CEP 2006-091-Rev 00;
Simvastatin Butylated hydroxy anisole 0.18-0.22% R1-CEP 2007-155-Rev 01;
Simvastatin Antioxidant Butylated Hydroxy Toluene 0.01% R1-CEP 2003-257-Rev 03
Others:
This supplier should not be approved in any new/ongoing applications. Each
involved NCA should evaluate if the supplier should be removed from existing
MAs.
An additional comment points out that the manufacturer also
produces an antibiotic for the French market. This API was not within the scope
of the inspection...
Besides,
the Spanish
authority has also published two GMP Non-Compliance Statements: one for a
Chinese API manufacturer, the other one for a Spanish medicinal products
manufacturer.
The CEP of the
Chinese company (JINAN JINDA PHARMACEUTICAL CHEMI. CO LTD in Shandong) was
withdrawn in 2015 already. It turned out the CAPA measures promised after the
inspection hadn't been implemented satisfyingly. In total, the Spanish
authority identified 2 critical and 8 major deficiencies, whereby the critical
deviations concerned the safety and control of raw data as well as OOS
assessments. Among other things, the main deficiencies concerned process and
cleaning validation.
Regarding the
Spanish manufacturer of liquids (ALCOR, S.L. in Guadalajara), the
lack of resources, facilities, personnel and materials has been particularly
criticised. The CAPA proposed were considered not appropriate by the authority
who sees the accumulation of tasks and responsibilities in some personnel as a
risk to quality.
Last but not least,
the British Authority (MHRA) also wrote a GMP Non-Compliance Statement. Here,
an Indian manufacturing site of Hospira Healthcare that manufactures
sterile medicinal products (lyophilisates, small-volume liquids and aseptically
filled powders) was concerned. For the MHRA, the conclusion to the many
deficiencies discovered there (e.g. inappropriate room segregation and
classification, deviating media fills without any root cause finding,
etc.) can be reduced to one causal point: a lack of scientific knowledge.
Source: EMA, gmp compliance
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