EN    EN  
 EUROPEAN  
COMMISSION 
Brussels, XXX   
[…](2017) XXX  draft 
  
COMMISSION DELEGATED REGUL ATION (EU) No …/.. 
of XXX  
supplementing Regulation (EU) No 536/2014 of the European Parliament and Council 
by specifying principles of and guidelin es for good manufacturing practice for 
investigational medicinal products for hu man use and arrangements for inspections 
(Text with EEA relevance) 
  
EN 2   EN EXPLANATORY MEMORANDUM 
1. CONTEXT  OF THE  DELEGATED  ACT 
A new Regulation (EU) No 536/2014 of the Eu ropean Parliament and of the Council 
of 16 April 2014 on clinical trials on medicinal products for human use, and 
repealing Directive 2001/20/EC1 will replace the current Di rective 2001/20/EC of the 
European Parliament and of the Council of 4 April 2001 on the approximation of the 
laws, regulations and administ rative provisions of the Member States relating to the 
implementation of good clinical practice in the conduct of clin ical trials on medicinal 
products for human use2.  
Commission Directive 2003/94/EC  of 8 October 2003 laying down the principles and 
guidelines of good manufacturing practice in  respect of medicinal products for 
human use and investigational me dicinal products for human use3 covers both 
"finished" medicinal products for human us e and investigational medicinal products 
for human use. Directive 2003/94/EC will not  apply to clinical trials conducted 
according to Regulation (EU) No 536/2014 and to ensure that investigational medicinal products used for those clinical trials, new provisions for good manufacturing practice for i nvestigational medicinal products for human use are 
necessary. 
Regulation (EU) No 536/2014 requires that  the Commission shall adopt delegated 
acts to specify the principles and guidelines of good manufacturing practice for 
ensure the quality of investigationa l medicinal products for human use and 
arrangements for inspections. 
2. CONSULTATIONS
 PRIOR  TO THE  ADOPTION  OF THE  ACT 
With a view to preparing this Delegate d Regulation, the Commission discussed with 
the ad hoc group on clinical tr ials, the expert group for th is Delegated Regulation, at 
its meetings on 1 December 2014 and on 8 February 2016. The ad hoc group on 
clinical trials were consulted in  a written procedure in April 2016. 
Furthermore, Member States experts on Good Manufacturing Pract ice of medicinal 
products in the context of the Good Ma nufacturing Practice/ Good Distribution 
Practice Inspectors Working Group were  also consulted in March 2015. 
A public consultation took place from 28 A ugust to 24 November 2015. In the public 
consultation, 26 responses were received from stakeholder orga nisations, individual 
companies, regional authorities and nationa l competent authorities in Europe and 
outside of Europe. 
3. LEGAL  ELEMENTS  OF THE  DELEGATED  ACT 
The legal basis for this Delegated Regula tion is Article 63(1) of Regulation (EU) 
No 536/2014. 
This Delegated Regulation supplements Regulation (EU) No 536/2014 by specifying 
the principles and guidelines of good ma nufacturing practice in respect of 
investigational medicinal products for human  use and arrangements for inspections.  
                                                 
1 OJ L 158, 27.5.2014, p. 1. 
2 OJ L 121, 1.5.2001, p. 34. 
3 OJ L, 262, 14.10.2003, p. 22.  
EN 3   EN COMMISSION DELEGATED REGU LATION (EU) No …/.. 
of XXX  
supplementing Regulation (EU) No 536/2014 of the European Parliament and Council 
by specifying principles of and guidelin es for good manufacturing practice for 
investigational medicinal products for hum an use and arrangements for inspections 
(Text with EEA relevance) 
THE EUROPEAN COMMISSION, 
Having regard to the Treaty on the Functioning of the European Union, Having regard to Regulation (EU) No 536/2014 of the European Parliament and of the 
Council of 16 April 2014 on clinical trials on  medicinal products for human use, and 
repealing Directive 2001/20/EC
4, and in particular Ar ticle 63(1) thereof, 
Whereas:  (1) The good manufacturing practice for investiga tional medicinal products for human use 
ensures that there is consistency between ba tches of the same inve stigational medicinal 
product used in the same or different clin ical trials, and that changes during the 
development of an investig ational medicinal product are adequately documented and 
justified. The manufacturing of  investigational medicinal products presents additional 
challenges comparing to the manufacturing of  authorised medicinal products because 
there are no fixed routines, ther e is a variety of clinical tr ial designs and consequently 
packaging designs. Those challenges are due to the need, often, of randomisation and 
disguise the identity of the investigati onal medicinal products for the purpose of 
clinical trial (blinding). The toxicit y, potency and sensitising potential of 
investigational medicinal pr oducts for human use may not be fully understood at the 
time of the trial, and the need to minimise all risks of cross-contamination is therefore of even greater importance than for author ised medicinal products. Because of this 
complexity, the manufacturing operations sh ould be subject to a highly effective 
pharmaceutical quality system. 
(2) Good manufacturing practice as  regards both medicinal pr oducts authorised to be 
placed on the market and investigational medicinal products are based on the same 
principles. The same manufacturing sites wi ll often manufacture both investigational 
and medicinal products authorised to be placed on the market. For that reason the 
principles and guidelines of good manufacturin g practice for investigational medicinal 
products for human use should be aligned as mu ch as possible with those applicable to 
medicinal products for human use. 
(3) In accordance with Article 61(5) of Regula tion (EU) No 536/2014 certain processes do 
not require the authorisation referred to in Arti cle 61(1) of that Regulation. In line with 
Article 63(2) of Regulation (EU) No  536/2014 good manufacturing practice for 
investigational medicinal products doe s not apply to those processes.  
                                                 
4 OJ L 158, 27.5.2014, p. 1.   
EN 4   EN (4) For the manufacturer to be able to co mply with good manufacturing practice for 
investigational medicinal products, coopera tion between the manufacturer and the 
sponsor is necessary. Likewise, for the spons or to comply with the requirements of 
Regulation (EU) No 536/2014 cooperation with the manufacturer is necessary. Where 
the manufacturer and the sponsor are differe nt legal entities, th e obligations of the 
manufacturer and sponsor vi s-à-vis each other should be specified in a technical 
agreement between them. Such an agreem ent should provide for the sharing of 
inspection reports and exchange of information on quality issues. 
(5) Investigational medicinal products imported into the Union should be manufactured by 
applying quality standards at least equivalent to those in  the Union. For those reasons, 
only products manufactured by a third country ma nufacturer that is entitled to do so in 
accordance with the laws of the country wh ere the manufacturer is  located, should be 
allowed to be imported into the Union.  
(6) All manufacturers should operate an eff ective quality assurance system of their 
manufacturing or import operations. Such a syst em in order to be effective requires the 
implementation of a pharmaceutical quality  system. Good documentation constitutes 
an essential part of quality assuran ce system. The documentation system of 
manufacturers shall enable the history of  the manufacture of each batch and any 
changes introduced during the development of  an investigational medicinal product to 
be traced. 
(7) Principles and guidelines of  good manufacturing practice for investigational medicinal 
products should be set out in  relation to quality management, personnel, premises, 
equipment, documentation, production, qu ality control, out sourced operations, 
complaints and recall, and self-inspections. 
(8) It is appropriate to require a product spec ification file which brings together and 
contain all of the essential reference do cuments to ensure th at investigational 
medicinal products are manufactured acco rding to good manufacturing practice for 
investigational medicinal products and the clinical  trial authorisation.  
(9) Due to the special characteristics of a dvanced therapy investigational medicinal 
products, the provisions on good manufacturing practice should be adapted to those 
products in accordance with a risk-based ap proach. As regards the advanced therapy 
medicinal products marketed in the Union, Article 5 of Regulat ion (EC) No 1394/2007 
of the European Parliament and of the Council5 provides for such adaptation. The 
Commission guidelines referred to in Ar ticle 5 of Regulati on (EC) No 1394/2007 
should also set out the requirements on good manufacturing practice applicable to 
advanced therapy investigat ional medicinal products. 
(10) In order to ensure conformity with  the principles and guidelines of good 
manufacturing practice for investiga tional medicinal products, provisions on 
inspections by the competent authorities of the Member States should be established. 
Member States should not be obliged to  inspect third country manufacturers of 
investigational medicinal products routinely. The need for such inspections should be 
established according to a risk based appro ach but third country manufacturers should 
be inspected at least if there is a suspici on that the investigati onal medicinal products 
                                                 
5 Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 
on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) 
No 726/2004 (OJ L 324, 10.12.2007, p. 121).   
EN 5   EN are not manufactured by applyi ng quality standards at l east equivalent to those 
applicable in the Union. 
(11) Inspectors should consider the Commissi on guidelines on good manufacturing practice 
for investigational medicinal products for hum an use. To achieve and maintain mutual 
recognition of inspection findings in the Un ion and facilitate the cooperation of the 
Member States, commonly recognised standards on the conduct of inspections on good manufacturing practice for investigational medicinal products in the form of 
procedures should be developed. The Comm ission guidelines and these procedures 
should be maintained and regularly update d, according to technical and scientific 
developments. 
(12) During inspections of a site the inspectors should check whether a site respects good 
manufacturing practice as regards both investigationa l medicinal products and 
medicinal products authorised to be placed on the market. For that reason, and in order 
to ensure the effective supe rvision, procedures and powers to carry out inspections to 
verify that good manufacturi ng practice for investigatio nal medicinal products for 
human use is followed should be aligned as much as possible to those for medicinal 
products for human use.  
(13) To ensure that inspections are effec tive, inspectors should be appropriately 
empowered.   
(14) Member States should be able to take action in case of non-compliance with good 
manufacturing practice for investigationa l medicinal products for human use.  
(15) The competent authorities should be required to set up quality systems to ensure that 
the inspection procedures are observed and consistently monitored. A well-functioning 
quality system should comprise an organi sational structure, clear processes and 
procedures, including standards operating pr ocedures to be followed by inspectors 
when performing their tasks, clearly defi ned details of the inspectors' duties and 
responsibilities and ongoing training requireme nts, as well as ad equate resources and 
mechanisms which aim to eliminate non-compliance.  
(16) This Regulation should apply from the sa me date as Commission Directive (EU) 
…/…
6,  
HAS ADOPTED THIS REGULATION: 
CHAPTER I 
GENERAL PROVISIONS  
Article 1 
Subject matter  
This Regulation specifies the principles a nd guidelines of good manuf acturing practice for 
investigational medicinal products for human us e the manufacture or impor t of which requires 
an authorisation as referred to in Article 61(1) of Regul ation (EU) No 536/2014 and lays 
down arrangements for inspections of manuf acturers in relation to compliance with good 
manufacturing practice in accordance w ith Article 63(4) of that Regulation. 
                                                 
6 [Commission Directive (EU) …/… supplementing Directive 2001/83/EC of the European Parliament 
and of the Council as regards the principles and guidelines of good manufacturing practice for 
medicinal products for human use (OJ …).].   
EN 6   EN Article 2 
Definitions  
For the purposes of this Regulation, th e following definitions shall apply: 
(1) 'manufacturer' means any person engaged in activities for which an authorisation is 
required in accordance with Article 61(1) of Regulation (EU) No 536/2014;  
(2) 'third country manufacturer' means any pe rson established in a third country and 
engaged in manufacturing opera tions in that third country 
(3) 'product specification file' means a referenc e file containing, or referring to files 
containing, all the information necessary to  draft detailed written  instructions on 
processing, packaging, quality control, testi ng and batch release of  an investigational 
medicinal product and to pe rform batch certification; 
(4) ‘validation’ means action of proving, in accordance with the principles of good 
manufacturing practice, that any procedure, process, equipment, material, activity or 
system actually leads to the expected results. 
CHAPTER II 
GOOD MANUFACTURING PRACTICE  
Article 3 
Conformity with good manufacturing practice  
1. The manufacturer shall ensure that manuf acturing operations ar e carried out in 
accordance with good manufacturing practice for investigational medicinal products 
specified in this Regulation and subject to an authorisation as referred to in 
Article 61(1) of Regulation (EU) No 536/2014. 
2. When importing an investigational me dicinal products, the holder of the 
authorisation referred to in Article 61( 1) of Regulation (EU) No 536/2014 shall 
ensure that the products have been manu factured by applying quality standards at 
least equivalent to those laid down by th is Regulation and in Regulation (EU) No 
536/2014, and that the third count ry manufacturer is authoris ed to manufacture that 
investigational medicinal produc ts in that third country. 
Article 4 
Compliance with clinical trial authorisation  
1. The manufacturer shall ensure that all manufacturing operations for investigational 
medicinal products are carried out in accordance with the documentation and 
information provided by the sponsor pursu ant to Article 25 of Regulation (EU) 
No 536/2014 and as authorised in accordan ce with the procedure laid down in 
Chapter II, or if documentation and information was subsequently amended, in Chapter III of this Regulation.  
2. The manufacturer shall regul arly review his manufacturin g methods in the light of 
scientific and technical progress and expe rience gained by th e sponsor during the 
development of the investig ational medicinal product.  
The manufacturer shall inform the spons or of his reviews of the manufacturing 
methods.  
EN 7   EN Where, following a review, an amendment to  the clinical trial authorisation is 
necessary, the application for the amendmen t shall be submitted in accordance with 
Article 16 of Regulation (EU) No 536/2014 wher e the change to the clinical trial is a 
substantial modification or the amendment shall be carried out in accordance with 
Article 81(9) of that Regulation where the change to the clinical trial is not a 
substantial modification. 
Article 5 
Pharmaceutical quality system  
1. The manufacturer shall esta blish, implement and maintain effective organised 
arrangements to ensure that  the investigational medicina l products are of the quality 
required for their intended use. Those a rrangements shall include the establishment 
of a good manufacturing practice and a quality control.  
2. Senior management and personnel from differe nt departments shall participate in the 
establishment of the pharm aceutical quality system. 
Article 6 
Personnel 
1. At each manufacturing site, the manufacturer  shall have a sufficient number of 
competent and appropriately qualified personn el at his disposal to ensure that the 
investigational medicinal products are of th e quality required for their intended use.  
2. The duties of managerial and supervisory staff, including th e qualified persons, 
responsible for implementing and operating good manufactu ring practice shall be set 
out in their job descriptions. Their hierarchical relationshi ps shall be set out in an 
organisation chart. The organisation chart a nd the job descriptions  shall be approved 
in accordance with the manufacturer's internal procedures.  
3. The staff referred to in paragraph 2 shall be given sufficient authority to discharge 
their responsibility correctly. 
4. The personnel shall receive initial and on-goi ng training covering in particular the 
following areas: 
(a) the theory and application of the concept of pharmaceutical quality; 
(b) good manufacturing practice.  The manufacturer shall verify th e effectiveness of the training. 
5. The manufacturer shall establish hygiene programmes, including procedures relating 
to health, hygiene practi ce and clothing of personnel.  The programmes shall be 
adapted to the manufacturing operations to  be carried out. The manufacturer shall 
ensure that the programmes are observed.  
Article 7 
Premises and equipment 
1. The manufacturer shall ensure that pr emises and manufacturing equipment are 
located, designed, constructed, adapted and maintained to suit the intended 
operations.   
EN 8   EN 2. The manufacturer shall ensure that the premises and manufacturing equipment are 
laid out, designed and operated in such a way as to minimise risk of error and permit effective cleaning and maintenance in order to avoid contamination, cross 
contamination and any other adverse effect  on the quality of the investigational 
medicinal product. 
3. The manufacturer shall ensure  that those premises and equipment to be used for 
manufacturing operations which are critical to the quality of the investigational 
medicinal products are subjected to a ppropriate qualifica tion and validation. 
Article 8 
Documentation 
1. The manufacturer shall establish and maintain a documentation system recording the 
following, where appropriate having rega rd to the activit ies undertaken: 
(a) specifications; (b) manufacturing formulae; (c) processing and packaging instructions; (d) procedures and protoc ols, including procedures for general manufacturing 
operations and conditions;  
(e) records, in particular covering the various manufacturing operations performed 
and batch records; 
(f) technical agreements  (g) certificates of analysis;  The documents specific to any investigational medicinal product shall be consistent 
with the product specification file as relevant. 
2. The documentation system shall ensure th e data quality and integrity. Documents 
shall be clear, free from error and kept up to date.  
3. The manufacturer shall retain  the product specification f ile and batch documentation 
for at least five years after the completion or discontinuation of the last clinical trial 
in which the batch was used.  
4. When documentation is stored using electronic, photographic or other data 
processing systems, the manufacturer shall first validate the systems to ensure that 
the data will be appropriately stored dur ing the period of st orage laid down in 
paragraph 3. Data stored by t hose systems shall be made readily available in readable 
form. 
5. The electronically stored data shall be protected against unlawful access, loss or 
damage of data by technique s, such as duplica tion, back-up and transfer onto another 
storage system. Audit trails, meaning records of all relevant changes and deletions in 
those data shall be maintained. 
6. The documentation shall be provided to  competent authority upon request.   
EN 9   EN Article 9 
Production 
1. The manufacturer shall carry out produc tion operations in accordance with pre-
established instructi ons and procedures.  
The manufacturer shall ensure that ade quate and sufficient resources are made 
available for the in-p rocess controls and that all process deviations and product 
defects are documented and thoroughly investigated. 
2. The manufacturer shall take  appropriate technical or organisational measures to 
avoid cross contamination and mixing of s ubstances. Particular attention shall be 
paid to the handling of inve stigative medicinal products during and after any blinding 
operation. 
3. The manufacturing process shall be validat ed to the full extent, taking into account 
the stage of product development.  
The manufacturer shall identify the process step s that ensure the safety of the subject 
and the reliability and robustne ss of the clinical trial data  generated in the clinical 
trial. Those critical process steps shall be validated and regu larly re-validated.  
All steps in the design and development of the manufacturing process shall be fully 
documented.  
Article 10 
Quality control 
1. The manufacturer shall esta blish and maintain  a quality contro l system under the 
authority of a person who has the requisite  qualifications and is independent of 
production. 
That person shall have access to one or more quality control laboratories 
appropriately staffed and equipped to car ry out the examination and testing of 
starting materials and packaging materials and the testing of intermediate and 
finished investigational medicinal products. 
2. The manufacturer shall ensure that the quality control laboratories comply with 
Article 25(1) of Regulation (EU) No 536/2014.  
3. When investigational medicinal products  are imported from third countries, 
analytical control in the Un ion shall not be mandatory. 
4. During the final control of th e finished investigational me dicinal product, and before 
its release for use in clinical trials, the manufacturer shall take into account: 
(a) analytical results; (b) production conditions; (c) the results of in-process controls; (d) the examination of the manufacturing documents; (d) the conformity of the pr oduct with its specifications; 
(e) conformity of the product with the clinical tria l authorisation; 
(f) examination of the final finished packaging.  
EN 10   EN Article 11 
Retention of samples used for quality control 
1. The manufacturer shall retain sufficient samples of each batch of bulk formulated 
product, of key packaging components used for each finished investigational medicinal product batch and of each batch of finished investigational medicinal product for at least two year s after the completion or di scontinuation of the last 
clinical trial in which the batch was used. 
Samples of starting materials, other than solvents, gases or water, used in the 
manufacturing process shall be  retained by the manufactur er for at least two years 
after the release of the inve stigational medicinal product. However, this period may 
be shortened where the period of stability of  the starting material, as indicated in the 
relevant specification, is shorter.  
In all cases samples shall be maintained by the manufacturer at the disposal of the 
competent authority.  
2. Upon application of the manufacturer, the competent authority may grant a 
derogation from paragraph 1 in relation to  the sampling and rete ntion of starting 
material and for certain products manufactured  individually or in small quantities, or 
when their storage could raise special problems. 
Article 12 
Responsibilities of the qualified person  
1. The qualified person referred to in Article 61(2)(b) of  Regulation (EU) No 536/2014 
shall be responsible for the following:  
(a) where investigational medicinal pro ducts are manufactured in the Member 
State concerned, verifying that each production batc h has been manufactured 
and checked in compliance with the requirements of good manufacturing practice for investigational medicinal pr oducts laid down in this Regulation and 
the information provided pursuant to  Article 25 of Regulation (EU) 
No 536/2014, taking into account the guideline s referred to in Article 63(1) of 
that Regulation; 
(b) where investigational me dicinal products are manufact ured in a third country, 
verifying that each pro duction batch has been manu factured and checked in 
accordance with quality standa rds at least equivalent to  those laid down in this 
Regulation and the information provided pursuant to Article 25 of Regulation 
(EU) No 536/2014 taking into account the guidelines referred to in Article 63(1) of that Regulation.  
The qualified person shall cer tify in a register or equivalent document provided for 
that purpose that each production batch comp lies with the requirements laid down in 
paragraph 1.  
2. The register or equivalent document shall be  kept up to date as operations are carried 
out and shall remain at the disposal of the competent authority for at least five years 
after the completion of or the formal discontin uation of the last clinical trial in which 
the product batch was used.   
EN 11   EN Article 13 
Outsourced operations 
1. Where a manufacturing operation or opera tion linked thereto is outsourced, the 
outsourcing shall be the subj ect of a written contract. 
2. The contract shall clearly lay down the res ponsibilities of each party. It shall lay 
down an obligation for the party to whom  the operations are outsourced to follow 
good manufacturing practice and set out the manner in which the qualified person 
responsible for certifying each batch is to discharge his responsibilities.  
3. The party to whom the opera tions are outsource d shall not subcontract any of the 
operations entrusted to him under the cont ract without written consent from the 
manufacturer. 
4. The party to whom the operations are outsour ced shall comply with [the principles 
and guidelines of good manufacturing pr actice applicable to the operations 
concerned and shall submit to inspections carried out by the competent authority 
pursuant to Article 63(4) of  Regulation (EU) No 536/2014. 
Article 14 
Complaints, product recall and emergency unblinding  
1. The manufacturer shall, in cooperation w ith the sponsor, implement a system for 
recording and reviewing complaints together with an effective system for recalling investigational medicinal products which have already entered the distribution 
network promptly and at any time. The manuf acturer shall record and investigate any 
complaint concerning a defect and shall inform the sponsor and the competent 
authority of the Member States concerned of any defect that could result in a recall or 
abnormal restriction on supply. 
All trial sites shall be identified and, in so far as possi ble, the countries of destination 
shall be indicated. 
In the case of an authorised investiga tional medicinal product, the manufacturer 
shall, in cooperation with the sponsor, in form the marketing authorisation holder of 
any defect that could be related to th at product. 
2. Where blinding of investigational medicinal pr oducts is required by the protocol of a 
clinical trial, the manufacturer shall im plement a procedure for the rapid unblinding 
of blinded products, where this is necessary  for a prompt recall as referred to in 
paragraph 1. The manufacturer shall ensure th at the procedure discloses the identity 
of the blinded product only in so far as it is necessary. 
Article 15 
Self-inspection by the manufacturer 
The manufacturer shall conduct regular inspections as part of the pharmaceutical quality 
system in order to monitor the implementati on and respect of good manufacturing practice. 
He shall take any necessary corrective action and to put in place any necessary preventive 
measures.  
The manufacturer shall maintain records of all such inspections and any corrective action or 
preventive measures subsequently taken.  
EN 12   EN Article 16 
Advanced therapy investigational medicinal products 
The good manufacturing principles shall be adap ted to the specific characteristics of the 
advanced therapy medicinal products when used as investigational medicinal products. 
Investigational medicinal products, which are at  the same time advanced therapy medicinal 
products, shall be manufactured in accordance with the guidelines referred to in Article 5 of 
Regulation (EC) No 1394/2007.  
CHAPTER III 
INSPECTIONS  
Article 17 
Supervision by inspection   
1. By means of regular inspections as referre d to in Article 63(4 ) of Regulation (EU) 
No 536/2014 the Member State shall ensure that holders of an authorisation as referred to in Article 61(1) of that Regul ation comply with the principles of good 
manufacturing practice laid down in this  Regulation and takes into account the 
guidelines referred in second subparagraph of Article 63(1) of Regulation (EU) 
No 536/2014].  
2. Without prejudice to any arrangements whic h may have been c oncluded between the 
Union and third countries, a competent authority may require  a third country 
manufacturer to submit to an  inspection as referred to in  Article 63(4) of Regulation 
(EU) No 536/2014 and this Regulation. This Regulation applies mutatis mutandis  to 
such inspections in third countries.  
3. Member States shall carry out inspections of third country manu facturers to ensure 
that investigational medici nal products imported into th e Union are manufactured by 
applying quality standards at least equivalent to those laid down in the Union.  
The Member States are not obliged to ro utinely inspect third country manufacturers 
of investigational medicinal products. The necessity of such inspections shall be 
based on an assessment of risk, but shall take place at least if the Member States have 
grounds for suspecting that the quality standa rds applied to the manufacture of the 
investigational medicinal products imported in to the Union are lower than those laid 
down in this Regulation and in the guidelin es referred to in the second subparagraph 
of Article 63(1) of Regulation (EU) No 536/2014. 
4. Inspections may, if necessary, be unannounced.  
5. Following an inspection, an inspection re port shall be drawn up by the inspector. 
Before the report is adopted by competen t authority, the manufacturer shall be 
afforded an opportunity to submit comments in  relation to the findi ngs of the report.  
6. Where the findings of the final report show  that the manufacturer complies with the 
good manufacturing practice fo r investigational medicina l products, the competent 
authority shall within a period of 90 days of the insp ection issue a ce rtificate of good 
manufacturing practice to the manufacturer. 
7. The competent authority shall enter the certificate of good manufacturing practice 
which they issue into the Union database re ferred to in Articl e 111(6) of Directive 
2001/83/EC.  
EN 13   EN 8. Where the outcome of the inspection is that the manufacturer does not comply with 
good manufacturing practice fo r investigational medicina l products, the competent 
authority shall enter this information into the Union database referred to in Article 111(6) of Directive 2001/83/EC.[   
9. The competent authority shall, upon receip t of reasoned request , send the inspection 
reports referred to in paragraph 4 electroni cally to the competent authorities of other 
Member States or to the European Medicines Agency ('the Agency').  
10. The competent authority shall enter the in formation relating to the authorisation 
referred to in Article 61(1) of Regulati on (EU) No 536/2014 in the Union database 
referred to in Article 111(6)  of Directive 2001/83/EC.  
Article 18 
Cooperation and coordination of inspections 
The competent authorities shall cooperate with each other and with the Agency in relation to 
inspections. They shall share information with  the Agency on both inspections planned and 
conducted.  
Article 19 
Recognition of inspection conclusions 
1. The conclusions reached in the inspection report referred to in Article 16(4) shall be 
valid throughout the Union. 
However, in exceptional cases, where a competent authority is unable, for reasons 
relating to public health, to recognise [the conclusions reached following an 
inspection under Article 63(4) of Regulat ion No 536/2014, that competent authority 
shall forthwith inform the Commission and the Agency. The Agency shall inform the other competent aut horities concerned.  
2. When the Commission is informed in accordance with the second subparagraph of 
paragraph 1, it may, after consulting the competent authority which was unable to 
accept the report, request the inspector w ho performed the insp ection to perform a 
new inspection. The inspector may be accompanied by two inspectors from other competent authorities which are not parties to the disagreement.   
Article 20 
Empowerments of the inspectors 
1. The competent authority shall provide in spectors with suitable means of their 
identification.  
2. Inspectors shall be empowered to: 
(a) enter and inspect the premises of the manufacturer and quality control 
laboratories having carried out check s pursuant to Article 10 for the 
manufacturer; 
(b) take samples, including for independen t tests to be carried out by an Official 
Medicines Control Laboratory or a la boratory designated fo r that purpose by 
the Member State, and  
EN 14   EN (c) examine any documents relating to the object of inspectio n, make copies of 
records or printed documents, print elec tronic records and take photos of the 
premises and equipment of the manufacturer. 
Article 21 
Competence and obligations of the inspectors 
1. The competent authority shall ensure that the inspectors possess adequate 
qualifications, experience and knowledge. In pa rticular, the inspectors shall have the 
following: 
(a) experience and knowledge of the inspection process; (b) the ability to make professional ju dgements as to the compliance with the 
requirements of good ma nufacturing practice; 
(c) ability to apply the principles  of quality risk management;  
(d) knowledge of current technologi es relevant for inspections;  
(e) knowledge of the current technol ogies for the manufacture of the 
investigational medicinal products. 
2. Information acquired as a result of in spections shall remain confidential. 
3. The competent authorities shall ensure that  inspectors receive the training necessary 
to maintain or improve thei r skills. Their training needs shall be assessed regularly 
by the persons appointed for that task. 
4. The competent authority shall document the qualifications, trai ning and experience 
of each inspector. Those records shall be kept up to date.  
Article 22 
Quality system   
1. The competent authorities shall establish, implement and comply with a properly 
designed quality system for their inspectors.  The quality system shall be updated as 
appropriate. 
2. Each inspector shall be informed of the standard operating procedures and of his 
duties, responsibilities and on-going training requirements. Those procedures shall be 
kept up to date. 
Article 23 
Impartiality of inspectors 
The competent authority shall en sure that inspector s are free of any undue influence that 
could affect their impartiality and judgment. 
Inspectors shall be independe nt, in particular, of:  
(a) the sponsor;  
(b) the management and personnel of  the clinical trial site;  
(c) the investigators involved in the clinical trials where th e investigational medicinal 
products manufactured by the inspected manufacturer are used;   
EN 15   EN (d) the persons financing the clinical trial in  which the investigational medicinal product 
is used; 
(e) the manufacturer. 
Inspectors shall make an annual declaration of th eir financial interests in  the parties inspected 
or other links to them. The comp etent authority shall take the declaration into consideration 
when assigning inspectors to specific inspections. 
Article 24 
Access to premises   
The manufacturer shall allow inspectors access to his premises and documentation at all 
times. 
Article 25 
Suspension or revocation of manufacturing authorisation 
If an inspection reveals that the holder of an authorisat ion as referred to in Article 61(1) of 
Regulation (EU) No 536/2014 fails  to comply with good manufactur ing practice as set out in 
Union law, the competent authority may, with  regard to this manufacturer, suspend 
manufacture or imports from third countries of  investigational medicinal products for human 
use, or suspend or revoke the authorisation for a category of preparations or all preparation. 
CHAPTER IV 
FINAL PROVISIONS  
Article 26 
Transitional provision 
The Member states may continue to apply national transposition measures adopted under 
Directive 2003/94/EC to the manufacture of investigational medici nal products used in 
clinical trials governed by Directive 2001/ 20/EC in accordance with the transitional 
provisions laid down in Article 98 of Regulation (EU) No 536/2014. 
Article 27 
Entry into force 
This Regulation shall enter into force on the twentieth day following that of its publication in 
the Official Journal of  the European Union . 
It shall apply from six months af ter the date of publication in the  Official Journal of the 
European Union of the notice referred to in Article 82(3) of Regulation (EU) No 536/2014 or 
1 April 2018, whichever is the later. 
This Regulation shall be binding in  its entirety and directly applicable in all Member States. 
Done at Brussels, 
 For the Commission 
 The President    
EN 16   EN   
 On behalf of the President    [Position]