Tuesday, May 28, 2019
Friday, May 10, 2019
ACE INHIBITORS
Introduction
ACE inhibitors are among the most widely prescribed cardiovascular medicines.
The ACE inhibitors are -
- Raipril
- Lisinopril
- Perndoprol
ACE inhibitors are used in the treatment of the following conditions :
- Hypertension - ACE inhibitors reduce the risk of serious cardiovascular events, such as heart attack and stroke. they may be used first or second line, usually usually in combination with another drugs.
- Ischemic heart disease - as with hypertension, the purpose of ACE inhibitors is to reduce the risk of heart attack and stroke.
- Chronic heart failure - used for the symptomatic treatments of heart failure, improving overall prognosis for the patients.
- Diabetic nephropathy - ACE inhibitors can be used to prevent nephropathy from progressing in diabetic patients. They may also be used for chronic kidney disease ( with proteinuria ) to reduce proeinuria.
ACE inhibitors are, then , an important class of cardiovascular medicines that play a significant clinical role hypertension, heat disease and kidney comlications.
Mechanism of action
The fundamental mechanism of ACE inhibitors pharmacology involve blocking the effect of ANGIOTENSIN CONVERTING ENZYME. The ACE enzyme is is predominantly found on the surface pulmonary and renal epithelia.
This enzyme is responsible for converting angiotensin I (ATI) to angiotensin I (ATI) Angiotensin I is itself produced from
angiotensinogen, a globular protein released from the liver in response to renin release from the kidney.
To summarize:
Renin is released from the juxtaglomerular apparatus of the
kidney in response to electrolyte and/or water imbalances in the body:
Low sodium levels
Low blood pressure
Decreased blood volume
Renin cleaves angiotensinogen intoATI.
Angiotensin-converting enzyme turns ATI into ATII.
Why is reducing angiotensin II levels important ?
- ATII stiulates the release of aldosterone from the adrenal cortex.
- In turn, aldosterone promotes reabsorption of sodiu and chloride ions, increasing water retention. During this process, potassium is also excreted.
- Vasoconstriction; increasing blood pressure.
- ADH secretion from posteriour lobe of the pituitary gland, prooting water retention from the collecting ducts.
ACE inhibitors, by preventing produvtion of ATII, has the following effects :
- Prevent aldosterone release from the adrenal cortex.
- Elimination of sodium ions ( and increased water loss ) from the kidney.
- Potassium ions are retained.
- Consequent reduction in blood volume and blood pressure
ACE inhibitors pharmmacolgy is dependent upon the cessation is dependent upon the
Tuesday, May 7, 2019
ICH
International council
for hormonisation of technical
Requirements for
pharmaceuticals for human use
It is an initiative that brings together regulatory
authorities and pharmaceutical industry to discuss scientific and technical
aspects of pharmaceutical product development and registration.
The mission of the ICH is
to promote public health by achieving greater harmonisation through the
development of technical Guidelines and requirements for pharmaceutical product
registration.
Hormonisation leads to a
more rational use of human, animal and other resources, the elimination of
unnecessary delay in the global development, and availability of new medicines
while maintaining safeguards on quality, safety, efficacy, and regulatory
obligations to protect public health.
ICH's mission is to
achieve greater harmonisation worldwide to ensure that safe, effective, and
high quality medicines are developed and registered in the most
resource-efficient manner. Harmonisation is achieved through the development of
ICH Guidelines via a process of scientific consensus with regulatory and
industry experts working side-by-side. Key to the success of this process is
the commitment of the ICH regulators to implement the final Guidelines.
ORGANISATION OF ICH
Process of Harmonisation
ICH harmonisation activities fall into 4 categories: Formal ICH Procedure, Q&A Procedure, Revision Procedure and Maintenance Procedure, depending on the activity to be undertaken. The development of a new harmonised guideline and its implementation (the formal ICH procedure) involves 5 steps
·
Consensus building
·
Confirmation of
consensus on the Technical Document
(b) Endorsement of draft Guideline by
Regulatory Members
·
Regulatory consultation and
discussion
Stage I - Regional
regulatory consultation
Stage II - Discussion of
regional consultation comments
Stage III - Finalisation
of Step 3 Experts Draft Guideline
·
Adoption of an ICH
Harmonised Guideline
·
Implementation
ICH Guidelines
The ICH topics are divided
into four categories and ICH topic codes are assigned according to these
categories.
QUALITY GUIDELINES
The quality
guidelines consists of chart of guidelines Q1 to Q14 which are described bellow
:
Q1A – Q1F STABILITY
Q1A
(R2) Stability testing of new drug substances and products
This Guideline provides recommendations on
stability testing protocols including
temperature,
humidity and trial duration for climatic Zone I and II. Furthermore, the
revised
document takes
into account the requirements for stability testing in Climatic Zones III and
IV in order to
minimise the different storage conditions for submission of a global dossier.
Q1B Stability testing : Photostability testing of new drug substances
and products.
The tripartite harmonised ICH Guideline was
finalised under Step
4 in November 1996.
This forms an
annex to the main stability Guideline, and gives guidance on the basic testing
protocol
required to evaluate the light sensitivity and stability of new drugs and
products.
Q1C Stability testing for new dosage forms
It extends the main stability Guideline
for new formulations of already approved medicines
and defines the
circumstances under which reduced stability data can be accepted.
Q1D Bracketing and matrixing designs for stability testing of new drug
Substances and
products
This document describes general principles for
reduced stability testing and provides
examples of
bracketing and matrixing designs.
Q1E Evaluation of stability data
This document extends the main Guideline by
explaining possible situations where
extrapolation
of retest periods/shelf-lives beyond the real-time data may be appropriate.
Furthermore, it provides examples of
statistical approaches to stability data analysis.
Q1F Stability data package of registration applications in climate zone
III and IV
The ICH Steering Committee endorsed the withdrawal of the Q1F
Guideline at its meeting
in Yokohama,
June 2006 and decided to leave definition of storage conditions in Climatic
Zones III and
IV to the respective regions and WHO.
Q2
Analytical Validation
Q2 (R2) /
Q14 Analyitical procedure development and revision of Q2(R1)
Analytical
validation
The
Q2(R2)/Q14 EWG will develop a new ICH Quality Guideline, ICH Q14, on
Analytical Procedure Development, and revise the ICH Q2(R1) Guideline on
Validation of Analytical Procedures, with a view to potentially combine
both
documents into one, for simplification and clarity.
Q2(R1) Revision
The scope of the revision of ICH Q2(R1) will include
validation principles that cover analytical use of spectroscopic or
spectrometry data (e.g., NIR, Raman, NMR or MS) some of which often require
multivariate statistical analyses. The guideline will continue to provide a
general framework for the principles of analytical procedure validation
applicable to products mostly in the scope of Q6A and Q6B.
These proposed guidelines (Q2(R2) and Q14) are intended to
complement ICH Q8 to Q12 Guidelines, as well as on-going ICH Q13 for Continuous
Manufacturing.
Q14 Analytical Procedure Development Guideline
The new guideline is proposed to harmonise the scientific
approaches of Analytical Procedure Development, and to provide the principles
relating to the description of Analytical Procedure Development process. This
new guideline is intended to improve regulatory communication between industry
and regulators and facilitate more efficient, sound scientific and risk-based
approval as well as post-approval change management of analytical procedures.
Q2 (R1) Validation of analytical procedures : text and methodology
This identifies
the validation parameters needed for a variety of analytical methods.
It also discusses the characteristics that must be considered during the
validation of the
analytical procedures which are included as part of registration
applications.
The tripartite harmonised ICH Guideline on Methodology (previously
coded Q2B) was
finalised under Step 4 in
November 1996. It extends the Guideline Q2A to include the actual experimental data required, along with the statistical
interpretation, for the
validation of analytical
procedures.
The Guideline on Methodology
has been incorporated into the Guideline on Text in
November 2005 and then renamed Q2(R1), without any changes in the
contents of the two Guidelines.
Q3A – Q3D Impurities
Q3A (R2) Impurities in new drug substances
The Guideline addresses
the chemistry and safety aspects of
impurities, including the
listing of impurities in specifications and
defines the thresholds for reporting,
identification and qualification.
The revision of the guideline has allowed
clarifying some
inconsistencies, to revise the decision tree,
to harmonize with Q3B and
to address some editorial
issues.
The
Attachment 2 of this guideline has been revised under Step 4
without further public consultation on 25 October 2006 (Q3A(R2))
Q3B
(R2) Impurities in new drug products
It complements the Guideline on
impurities in new drug substances and provides advice in regard to impurities
in products containing new, chemically synthesized drug substances. The
Guideline specifically deals with those impurities which might arise as
degradation products of the drug substance or arising from interactions between
drug substance and excipients or components of primary packaging materials. The
Guideline sets out a rationale for the reporting, identification and
qualification of such impurities based on a scientific appraisal of likely and
actual impurities observed, and of the safety implications, following the
principles elaborated in the parent Guideline. Threshold values for reporting
and control of impurities are proposed, based on the maximum daily dose of the
drug substance administered in the product.
The
Attachment 2 of this Guideline has been revised under Step 4 without further public consultation on 2 June 2006 (Q3B(R2)).
Q3C (R7) Impurities : Guidelines for residual solvents
This recommends the use of less toxic
solvents in the manufacture of drug substances and dosage forms, and sets
pharmaceutical limits for residual solvents (organic volatile impurities) in
drug products.
Maintenance Process
A
Maintenance process has been done to revise Permitted Daily Exposure (PDE), as
new toxicological data for solvents become available.
Limit values
for three residual solvents in drug products were revised on basis of the newly
recognised toxicity data; lower PDE for N-Methylpyrrolidone being kept in Class
2 (limited by health-basis) and for Tetrahydrofuran and Cumene being placed
into Class 2 from Class 3 (no health-based).
Both
revisions (PDE for THF and PDE for NMP) reached Step
4 of the process in September 2002. A corrigendum to
calculation formula for NMP was subsequently approved on 28 October 2002. As
per the new coding rule, they were incorporated into the core Guideline in
November 2005.
In February
2009, Table 2, Table 3 and Appendix 1 of the Core Guideline were updated to
reflect the revision of the PDEs for N-Methylpyrrolidone and Tetrahydrofuran
(Q3C(R4)).
In October 2016, the PDE for Methyl isobutyl ketone (MIBK) was revised,
and Triethylamine (TEA) was added as a news solvent. Based on new data, MIBK
was moved from Class 3 (solvents with low toxic potential) to Class 2 (solvents
to be limited). The new solvent Triethylamine was included in Class 3 (solvents
with low toxic potential) (Q3C(R6)).
In October 2018, the MC approved the error correction of the Permitted Daily Exposure (PDE) for ethyleneglycol (Q3C(R7)). Additionally, the MC approved the publication of Support Documents 1, 2 and 3, which include the summaries of the toxicity data from which PDEs were derived.
In October 2018, the MC approved the error correction of the Permitted Daily Exposure (PDE) for ethyleneglycol (Q3C(R7)). Additionally, the MC approved the publication of Support Documents 1, 2 and 3, which include the summaries of the toxicity data from which PDEs were derived.
Q3C
(R8) Impurities : Guidelines for residual solvents
The Q3C(R8) EWG is currently
undertaking a maintenance of the Guideline, which will result in the future
Q3C(R8) version, to develop PDE levels for three solvents:
2-methyltetrahydrofuran, cyclopentylmethylether and tert-butanol.
Q3D
(R1) Guidelines for elemental impurities
ICH Q3D Elemental Impurities is a quality guideline for the
control of elemental impurities in new drug products (medicinal products), and
it establishes Permitted Daily Exposures (PDEs) for 24 Elemental Impurities
(EIs) for drug products administered by the oral, parenteral and inhalation
routes of administration. In addition, guidance is provided in Q3D on how to
develop an acceptable level for EIs for drug products administered by other
routes of administration.
In March 2019, the Q3D(R1) Guideline, which was the result
of a revision of the PDE level for Cadmium by inhalation in the Q3D Guideline,
reached Step 4 of the ICH process.
Q3D
(R2) Revision
of Q3D (R1) for cutaneous and transdermal products
ICH
Q3D(R1) Elemental Impurities is a quality guideline for the control of
elemental impurities in new drug products (medicinal products), and it
establishes Permitted Daily Exposures (PDEs) for 24 Elemental Impurities (EIs)
for drug products administered by the oral, parenteral and inhalation routes of
administration. In addition, guidance is provided in Q3D(R1) on how to develop
an acceptable level for EIs for drug products administered by other routes of
administration.
The
Q3D(R2) Maintenance EWG is currently undertaking a maintenance of the Guideline
to develop PDE levels for cutaneous and transdermal products.
Maintenance
Process
A
Maintenance Procedure applies to revision of the Q3D(R1) Guideline for
Elemental Impurities. These changes includes the incorporation of Permitted
Daily Exposure (PDE) for new elemental impurities(EI)/routes of administration
and revising the PDE for EI already listed in Q3D(R1) as new toxicological data
for EI becomes available.
Products
administered on skin and its appendages (e.g., hair, nails) remain the largest
area where PDEs for EIs have not been established. In September 2016, the ICH
Management Committee approved the revision of the ICH Q3D Concept Paper to
include PDEs for the cutaneous and transdermal Route of Administration to
continue the process of harmonisation, where necessary. This leads to the
establishment of an Expert Working Group (EWG) to develop PDEs levels for all
24 EI included in the Q3D(R1) Guideline for products administered by the
cutaneous and transdermal routes of administration.
Q3D training Implementation of guideline for
elemental impurities
This Implementation Working Group (IWG)
was endorsed by the ICH Steering Committee in October 2014. Throughout the
development of the Q3D Guideline, external audiences, constituents and
interested parties have clearly communicated the complexity of the
implementation approaches for this guideline. While the Q11 Guideline provides
the framework, it cannot provide the detailed examples covering the breadth of
potential case studies for products within scope of the guideline.
Consequently, the ICH SC considered that the development of a comprehensive
training programme and supporting documentation sponsored by ICH was necessary
to ensure the proper interpretation and effective utilisation by industry and
regulators alike to enable a harmonised and smooth implementation of Q3D on a
global basis.
Q4 – Q4B PHAMEMACOPIEIAS
Q4 Pharmacopoeias
Q6A activity provided the framework on
how to set specifications for drug substances to address how regulators and
manufacturers might avoid setting or agreeing to conflicting standards for the
same product, as part of the registration in different regions. The
resulting ICH Q6A Guideline provides harmonised guidance in this area.
With the passage of the Chemical Substances (Q6A) ICH Guideline, the
harmonisation of several compendial test chapters has been considered as
critical by the ICH Steering Committee. These chapters are at various stages of
harmonisation among the three pharmacopeial organisations (USP, JP & EP).
The three organisations conduct their harmonisation efforts through a
tripartite pharmacopeial harmonisation program known as the Pharmacopoeial
Discussion Group (PDC).
Q4A Pharacopoeial Harmonisation
The pharmacopoeial authorities, working
together through the Pharmacopoeial Discussion Group (PDG), have been closely
involved with the work of ICH since the outset and harmonisation between the
major pharmacopoeias, which started before ICH, has proceeded in parallel. The
ICH Steering Committee receives regular reports on the status of pharmacopoeial
harmonisation at its meetings.
Q4B Evaluation and recommendation of
pharmacopoeial texts for use in
the ICH region
This document
describes a process for the evaluation and recommendation by the Q4B Expert
Working Group (EWG) of selected pharmacopoeial texts to facilitate their
recognition by regulatory authorities for use as interchangeable in the ICH
regions and since 2010 in Canada. Following favourable evaluations, ICH will
issue topic-specific annexes with information about these texts and their
implementation. Implementation of the Q4B annexes is intended to avoid
redundant testing by industry.
Given the nature of
this topic, no Concept Paper was developed for Q4B.
Q5A – Q5E
QUALITY OF BIOTECHNOLOGICAL PRODUCTS
Q5A (R1) Viral
safety evaluation of biotechnology products derived from cell
Lines of human or animal origin
This is concerned with testing and evaluation of the
viral safety of biotechnology products derived from characterised cell lines of
human or animal origin. The purpose is to provide a general framework for virus
testing experiments for the evaluation of virus clearance and the design of
viral tests and clearance evaluation studies.
(Please note that a typographic
error has been corrected on 23 September 1999 on Table A-1. the Genome of the
Reovirus 3 is RNA (and not DNA as previously printed). The correction was
integrated in the Guideline that was then renamed Q5A(R1)).
Q5B Analysis of the
expression construct in cells used for productions of
r-DNA derived
protein products
It advises on the types of information that are considered
valuable in assessing the structure of the expression construct used to produce
recombinant DNA derived proteins.
Q5C Stability testing
of biotechnological / Biological products
This document augments the stability Guideline (Q1A above)
and deals with the particular aspects of stability test procedures needed to
take account of the special characteristics of products in which the active
components are typically proteins and/or polypeptides.
Q5D Derivation and characterization of cell
substrates used for production
of biotechnological /
biological products
This document provides broad
guidance on appropriate standards for the derivation of human and animal cell
lines and microbes used to prepare biotechnological/biological products and for
the preparation and characterisation of cell banks to be used for production.
Q5E Comparability of biotechnological /
biological projects subjects to
changes in the manufacturing
process
The objective of this document is to provide principles for
assessing the comparability of biotechnological/biological products before and
after changes are made in the manufacturing process for the drug substance or
drug product. Therefore, this guideline is intended to assist in the collection
of relevant technical information which serves as evidence that the
manufacturing process changes will not have an adverse impact on the quality,
safety and efficacy of the drug product. The document does not prescribe any
particular analytical, nonclinical or clinical strategy. The main emphasis of
the document is on quality aspects.
Q6A – Q6B SPECIFICATIONS
Q6A Specifications : test procedure and
acceptance criteria for new drugs
substances and new drug
products : Chemical substances
This addresses the process of
selecting tests and methods and setting specifications for the testing of drug
substances and dosage forms. Account has been taken of the considerable
guidance and background information which are present in existing regional
documents.
Q6B Specifications : Test procedures and
acceptance criteria for
biotechnological / Biological
products
This document provides guidance on
justifying and setting specifications for proteins and polypeptides which are
derived from recombinant or non-recombinant cell cultures. The scope of this
part is initially limited to well-characterised biotechnological products,
although the concepts may be applicable to other biologicals as appropriate. In
view of the nature of the products, the topic of specifications include
in-process controls, bulk drug, final product and stability specifications and
give guidance for a harmonised approach to determining appropriate
specifications based on safety, process consistency, purity, analytical
methodology, product administration and clinical data considerations.
Q7 GOOD MANUFACTURING PRACTIVE
Q7 Good manufacturing practice guide for
active pharmaceutical
Ingredients
Early
in the ICH Process it was agreed that there was adequate international
agreement on the technical aspects of Good Manufacturing Practices (GMP) for
Pharmaceutical Products and that further harmonisation action through ICH was
not needed. Recently, however, attention has focused on the need to formalise
GMP requirements for the components of pharmaceutical products - both active
and inactive. In February 1998, the ICH Steering Committee agreed that GMP for
Active Pharmaceutical Ingredients (APIs) should be adopted as an ICH Topic.
When
this topic was adopted, the Steering Committee took steps to ensure that due
account was taken of the work already in progress by PIC/S, FDA, United
States and other parties. In view of the unusually wide implications of
this Topic, a much extended EWG has been established which includes, in
addition to the six ICH parties and the Observers, experts representing IGPA
(generics industry), WSMI (self medication industry) and PIC/S. With respect to
the latter representatives from China, India and Australia have been invited to
participate.
Q7
Q&As Questions and
Answer : GMP guide for active pharmaceutical
Ingredients
Experience gained with the implementation
of the ICH Q7 Guideline since its finalisation in 2000 shows that uncertainties
related to the interpretation of some sections exist. Technical issues with
regard to GMP of APIs – also in context with new ICH Guidelines - are addressed
in this Question and Answer document in order to harmonise expectations during
inspections, to remove ambiguities and uncertainties and also to harmonise the
inspections of both small molecules and biotech APIs.
Q8 PHARMACEUTICAL DEVLOPMENTS
Q8 (R2) Pharmaceutical developments
This
Guideline is intended to provide guidance on the contents of Section 3.2.P.2
(Pharmaceutical Development) for drug products as defined in the scope of
Module 3 of the Common Technical Document (ICH topic M4). The guideline does
not apply to contents of submissions for drug products during the clinical
research stages of drug development. However the principles in this guideline
are important to consider during these stages. This guideline might also be
appropriate for other types of products. To determine the applicability of this
guideline for a particular type of product, applicants should consult with the
appropriate regulatory authorities.
The
annex to the tripartite harmonised ICH text was finalised under Step 4 in
November 2008 and incorporated into the core Guideline, which was then renamed
Q8(R1).
The
annex provides further clarification of key concepts outlined in the core
Guideline. In addition, this annex describes the principles of quality by
design (QbD). The annex is not intended to establish new standards: however, it
shows how concepts and tools (e.g., design space) outlined in the parent Q8
document could be put into practice by the applicant for all dosage forms.
Where a company chooses to apply quality by design and quality risk management
(Q9: Quality Risk Management),
linked to an appropriate pharmaceutical quality system, then opportunities
arise to enhance science- and risk-based regulatory approaches (see Q10: Pharmaceutical Quality
System).
The Q8(R1) Guideline was revised in Summer 2009 to reflect
minor corrections to Example 2 on page 23 (Q8(R2)).
Q8/9/10
Q&As Q8/Q9/Q10 –
Implementation
Since reaching Step 4 and publication within the ICH regions,
experiences by all parties with the implementation of the ICH Q8(R2), Q9 and
Q10 Guidelines have resulted in the need for some clarification. The Questions
and Answers developed by the Quality Implementation Working Group (IWG) are
intended to facilitate the implementation of the Q8(R2), Q9 and Q10 Guidelines,
by clarifying key issues.
The document with the
first and second set of Q&As was finalised under Step 4 in April and June 2009, respectively.
In October 2009, a third set of Q&As was developed and
approved by the Steering Committee for integration in the Q&A document
(Q8/Q9/Q10 Q&As (R3)).
In November 2010, a fourth set of Q&As was developed and
approved by the Steering Committee for integration in the Q&A document
(Q8/Q9/Q10 Q&As (R4)).
implementation of Q8(R2), Q9 and Q10, which supplement the
existing Questions & Answers and workshop training materials already
produced by this group. The document with the first and second set of Points to
Consider Document was finalised in June and November 2011, respectively.
Q9 QUALITY RISK MANAGEMENT
This
Guideline provides principles and examples of tools of quality risk management
that can be applied to all aspects of pharmaceutical quality including
development, manufacturing, distribution, and the inspection and
submission/review processes throughout the lifecycle of drug substances and
drug (medicinal) products, biological and biotechnological products, including
the use of raw materials, solvents, excipients, packaging and labeling
materials.
Q10 PHARMACEUTICAL QUALITY SYSTEM
This Guideline applies to pharmaceutical
drug substances and drug products, including biotechnology and biological
products, throughout the product lifecycle.
The elements of Q10 should be applied in a manner that is appropriate and proportionate to each of the product lifecycle stages, recognising the differences among, and the different goals of each Stages.
The elements of Q10 should be applied in a manner that is appropriate and proportionate to each of the product lifecycle stages, recognising the differences among, and the different goals of each Stages.
Q11 DEVLOPMENT AND MANUFACTURING OF DRUG
SUBSTANCES
This new guidance is proposed for Active
Pharmaceutical Ingredients (APIs) harmonising the scientific and technical
principles relating to the description and justification of the development and
manufacturing process of Drug Substances
including both chemical entities and biotechnological/biological entities.
QUESTIONS & ANSWERS : Section and
justification of starting materials for the manufacturure of drug substances
Implementation
of the ICH Q11 Guideline and its recommendations on the development and
manufacture of drug substances has given rise to requests for clarification
relating to the selection and justification of starting materials.
The
Q11 Implementation Working Group (IWG), established by ICH in 2014, developed a
Questions and Answers (Q&A) document which reached Step 2b of the ICH
Process in November 2016. These Q&As are intended to provide additional
clarification and to promote convergence on the considerations for the
selection and justification of starting materials and on the information that
should be provided in marketing authorisation applications and/or Master Files.
The focus of the Q&A document is on chemical entity drug substances.
Q12 LIFECYCLE MANAGEMENT
Technical and regulatory
consideration of pharmaceutical products lifestyle management
This new guideline is proposed to provide
guidance on a framework to facilitate the management of post-approval
Chemistry, Manufacturing and Controls (CMC) changes in a more
predictable and efficient manner across the product lifecycle. Adoption
of this new ICH Guideline will promote innovation and continual improvement,
and strengthen quality assurance and reliable supply of product, including
proactive planning of supply chain adjustments. It will allow regulators
(assessors and inspectors) to better understand the firms Pharmaceutical
Quality Systems (PQSs) for management of post-approval CMC changes. This new
guideline is intended to complement the existing ICH Q8 to Q11 Guidelines, and
includes a core Guideline as well as Annexes.
Q13 CONTINEOUS MANUFACTURING OF DRUG
SUBSTANCES AND DRUG PRODUCTS
This
new Guideline is proposed to:
•
Capture key technical and regulatory considerations that promote harmonisation,
including certain Current Good Manufacturing Practices (CGMP) elements specific
to Continuous Manufacturing (CM),
• Allow drug manufacturers to employ flexible approaches to develop, implement, or integrate CM for the manufacture – drug substances and drug products – of small molecules and therapeutic proteins for new and existing products,
• Provide guidance to industry and regulatory agencies regarding regulatory expectations on the development, implementation, and assessment of CM technologies used in the manufacture of drug substances and drug products.
• Allow drug manufacturers to employ flexible approaches to develop, implement, or integrate CM for the manufacture – drug substances and drug products – of small molecules and therapeutic proteins for new and existing products,
• Provide guidance to industry and regulatory agencies regarding regulatory expectations on the development, implementation, and assessment of CM technologies used in the manufacture of drug substances and drug products.
Q14 ANALYTICAL PROCEDURE DEVLOPMENT
Work on the
development of the Q14 Guideline on Analytical Procedure Development is
performed by the Q2(R2)/Q14 EWG.
