control strategy as the keystone of the product lifecycle, from

Control Strategy

JANUARY/FEBRUARY 2012 PHARMACEUTICAL ENGINEERING Online Exclusive 1

Online Exclusive from PHARMACEUTICAL ENGINEERING®

The Of�cial Magazine of ISPE

January/February 2012, Vol. 32 No. 1

www.PharmaceuticalEngineering.org ©Copyright ISPE 2012

This article

presents

the general

principles of

Control Strategy

(CS) and its

evolution. A

method for

designing a CS

and its �ling

in Common

Technical

Document

(CTD) format

are proposed.

CS within the

continuous

process

veri�cation and

product lifecycle

is discussed.

Control Strategy as the Keystone of the Product Lifecycle, from Product/Process Understanding to Continuous Process Veri�cation and Improvement

by Johanne Piriou, Bernard Elissondo, Michel Hertschuh,

and Roland Ollivier

IntroductionAccording to the ICH Q10 guideline, Control

Strategy is a planned set of controls, derived

from current product and process understanding

that assures process performance and product

quality. Control Strategy includes different

types of control proposed by the applicant to

assure product quality, such as in-process test-

ing and end product testing. It ensures that the

manufactured product has the quality attributes

that impact the safety, efficacy, and quality of

the product used for the patient.1,2,3

The Control Strategy has always been a

requirement, but this concept has evolved with

the implementation of ICH guidelines.4,5 In a

traditional approach to manufacturing process

development, Control Strategy describes a set of

controls, ensuring, as a whole, the product qual-

ity and the control of the sources of variability.

In an enhanced approach to manufacturing

process development using Quality by Design

(QbD) concepts as seen in Figure 1, Control

Strategy is based on a better understanding of

the product and the process allowing to identify

which material attributes and process param-

eters should be controlled. Scientifically sound

and based on risk assessment, this approach

allows Control Strategy to focus on components

having an effect on product Critical Quality At-

tributes (CQAs). A CQA is defined as a physical,

chemical, biological, or microbiological property

or characteristic that should be within an appro-

priate limit, range, or distribution to

ensure the desired product quality.4

Traditional and enhanced ap-

proaches to manufacturing process

development are not mutually exclu-

sive. For existing products, without

a manufacturing process developed

in a QbD approach, Control Strategy

can be designed on a combination of

both knowledge sources, traditional or

enhanced, for control of CQAs, steps,

or unit operations.

This article deals with the benefits

of the implementation of a Control

Strategy based on an enhanced ap-

proach of the manufacturing process

development that generates a better

product and process understanding.

It shows how the QbD approach can

provide pertinent data to design an

Figure 1. The Quality

by Design concepts

(adapted from Moheb M.

Nasr, CDER/FDA, 2010).

2 PHARMACEUTICAL ENGINEERING Online Exclusive JANUARY/FEBRUARY 2012

Control Strategy

efficient Control Strategy allowing more flexibility to submit

it in the regulatory file in CTD format. Finally, it discusses

how the Control Strategy plays a central role in the product

lifecycle by acting as a major component of continual improve-

ment.

Key Concepts of Control StrategyThe demonstration that a manufacturing process ensures

that the final product meets its quality criteria has always

been a requirement. Nevertheless, with the higher complexity

of new pharmaceutical products and processes, an improve-

ment of the Control Strategy became necessary to explain

and justify how the product quality is managed. To meet

this goal, a detailed description of each mode of control used

for each CQA must be provided. In addition, an overview of

Control Strategy should provide an understanding of how all

these ways of control collectively ensure the product quality.

ICH guidelines Q8,4 Q9,8 Q10,9 and Q115 and the reflections

around their concrete implementation10,11 reinforced the need

for improvement in Control Strategy.

The parent guideline on Pharmaceutical Development

ICH Q8(R2)4 introduced the concept of Control Strategy and

its link with the control of product critical attributes. This

guideline explains that “the process control strategies that

provide process adjustment capabilities to ensure control of

all critical attributes should be described.” The ICH Q109

guideline published in 2008 goes further in the principles

of this concept, defining the Control Strategy as “a planned

set of controls, derived from current product and process un-

derstanding that ensures process performance and product

quality. The controls can include parameters and attributes

related to drug substance and drug product materials and

components, facility and equipment operating conditions,

in-process controls, finished product specifications, and the

associated methods and frequency of monitoring and control.”

ICH Q10 integrates Control Strategy as part of the process

performance and product quality monitoring system through-

out the product lifecycle.

Designing and defining an efficient Control Strategy

was made possible in 2009 with the publication of the ICH

Q8(R2),4 describing the concepts of Quality by Design, con-

sistent with the new FDA vision. The Control Strategy can

indeed be designed on the outputs of QbD approach to product

development. For the first time, this guideline establishes a

well-developed Control Strategy based on product knowledge

and process understanding in combination with quality risk

management.9 The guide Q8(R2) focuses on the identification

of the sources of variability that can impact downstream

process steps, in-process materials, and finally drug product

quality. The key concept for designing an appropriate Control

Strategy is to identify and understand the linkage between

material attributes and process parameters to product CQAs.

This guide highlights an opportunity to shift controls upstream

and to minimize the need for end product testing.

The ICH Q115 guide, published for consultation (step 3)

extends application of Quality by Design concepts to the drug

substance. It clarifies the possibility for regulatory flexibil-

ity, and gives a central role to the Control Strategy. Overall,

Control Strategy appears as a keystone allowing:

process acquired during development

variability of the product and the process is managed

process performance throughout the lifecycle

Furthermore, ICH Q11 focuses on the existence of two ap-

proaches to pharmaceutical development: the “traditional”

one and the “enhanced” one. The guide underlines that the

combination of the two approaches is possible.

Bene�ts of Control Strategyin a QbD Approach

Every drug substance and drug product, whether developed

through a traditional or an enhanced approach, has an as-

sociated Control Strategy; therefore, Control Strategy is

designed and justified through a traditional or an enhanced

approach or a combination of both. Utilizing the traditional

way for some CQAs, steps, or unit operations, and a better-

developed approach for others, for which the knowledge and

understanding are wider, is allowed.

As shown in Figure 2, in the traditional approach to Control

Strategy, drug product quality is generally controlled primarily

by input materials (source and auxiliary), intermediates (in-

process materials), and end product testing. Control of process

is realized through in-process controls. Process reproducibility

is “demonstrated” by process validation and change control

ensures the maintenance of the product and process “state of

control.” This conventional approach can be considered as a

minimal approach. It presents the following issues, detailed

below, mainly based on the lack of product/process linkage

understanding.

First, if the Control Strategy is mainly based on product

testing (end product and materials), it is necessary to demon-

strate that the analytical methods are appropriate, justifying

their reliability and relevance. Indeed, if the analytical testing

is not appropriate for the demonstration of a CQA control

(i.e., the CQA remains within its specifications), additional

control must be considered. Therefore, input and in-process

materials testing are usually added, as well as process con-

Figure 2. An example of Control Strategy in a traditional approach

of development.

Control Strategy


trol through in-process controls. But with a reduced product/

process knowledge and understanding, the linkage between

input materials control, in-process controls, and final product

quality is quite empirical. How do you ensure that a control

performed at a certain step of the process ensures the final

CQA range? How do you bring the scientific evidence that

other process steps do not impact the product when knowledge

is tight?

Control Strategy based on the traditional approach usually

includes demonstration of process reproducibility through

process validation for which it is difficult to propose scientific

targets and criteria with a limited product/process character-

ization.

Finally, the change control process is used to ensure that

the product and process are kept in a state of control. But

how do you scientifically demonstrate the non impact of the

change with limited knowledge? The traditional Control

Strategy approach provides limited flexibility to address

variability (for example, raw materials variability), set points,

and operating ranges are set narrowly to ensure consistency

of the manufacturing process and product quality.5

These issues and questions are addressed by the enhanced

development approach, using Quality by Design. QbD provides

the keys to design an appropriate Control Strategy based on

better product and process understanding and on identification

of the sources of variability in a more systematic way. Drug

product quality is ensured by risk-based Control Strategy

enabled by well understood linkages between input mate-

rial attributes and process parameters to output material

attributes. Figure 3 shows one example of what a Control

Strategy can include in the enhanced approach.

This knowledge can provide flexibility in the operating

ranges for process parameters to address variability. Thus,

quality controls can be shifted upstream with the possibility

of real-time release testing, reduced end product testing, or

any combination thereof.

Design of Control Strategyin the Enhanced (QbD) Approach

In accordance with the QbD concepts expressed in ICH Q8(R2)4

and ICH Q115, the Control Strategy approach is becoming

explicit. The first principle is to understand that a Control

Strategy, in the enhanced approach, is an iterative process,

reviewed as the level of understanding increases during the

product lifecycle. Figure 3 shows a schematic view of Control

Strategy elements in the enhanced approach.

In the design of Control Strategy, the first step is the prod-

uct description and characterization to identify the product

quality attributes that answer to the Quality Target Product

Profile (QTPP). (If we take an example of protein purification

process, the protein safety is ensured in particular by the CQA

“content of impurity X.” This example is developed in italis, at

each step of the approach described in this section.)

From the quality attributes, the identification and assess-

ment of the critical quality attributes is performed using

risk-based tools. In front of the complexity of pharmaceutical

products, the classification and prioritization of the CQAs

becomes necessary, by assessment of the quality risk on

product safety and efficacy. Not only necessary for product/

process development to prioritize the development studies

to increase product knowledge, this prioritization is also

needed for Control Strategy justification. Indeed, a CQA that

presents a high level of risk on patient safety (e.g., sterility

for parenteral products) and product efficacy (e.g., protein

activity) should be tightly controlled, and might require

multiple control points. Furthermore, the ability of individual

controls to detect a potential problem with relevance and reli-

ability must be demonstrated. This can be difficult to assess

for functional or characterization assays that can be part of

the Control Strategy, but should be confirmed by subsequent

control points.

The additional control points require process description

and characterization to determine the links between product

CQAs, process parameters, and material attributes. It is es-

sential, for each process step, to identify the input materials

attributes (source and auxiliary materials), the output ma-

terials attributes (also called in-process materials), and the

process parameters. Then, it is necessary to characterize if

these attributes and parameters, at this step, can impact the

end product quality. The process parameters and in-process

material attributes are classified and ranked as critical for

product quality or key for processability as seen in Table A,

using quality risk assessment.

See below (in italics) an example of a Control Strategy

element: it concerns a protein purification process with two

purification steps, one Ionic Exchange Chromatography (IEC)

and one filtration step. Only the IEC impacts the CQA “content

of impurity X.” Content of impurity X in Intermediate n°1

(input material of IEC step) and in Intermediate n°2 (output

of IEC step) are critical in-process materials. IEC medium

is auxiliary material attribute that impacts the CQA. The

material attributes impacting the CQAs, which control takes

part in the Control Strategy, are listed in Table A.The process

parameters of IEC, listed in Table B, are 1. linear flow rate, Figure 3. An example of a Control Strategy in an enhanced

approach of development (QbD).


Control Strategy

2. protein load volume/column volume ration, 3. column bed

height. Linear flow rate presents high level of risk for this

CQA.

The risk assessment of each input material, with regard

to the process step where it is used, is essential to evaluate

if its quality must be tightly controlled or if there are down-

stream process steps that can address the material variabil-

ity. It is built on quality impacts (patient risk) on one side,

and processability (manufacturability) impacts on the other

side. It is the same method for the in-process materials, in

order to determine if at one process step, the attributes must

be controlled or not. If the in-process material attribute is

important for processability only, the accurate control point

that ensures the CQA range has to be implemented later in

the process, at a step where it becomes critical to obtain the

final target.

After this quality risk assessment, for each Critical Process

Parameter (CPP), critical input material attribute, critical

in-process material attribute identified, a Control Strategy is

proposed in order to ensure that the associated CQA is kept

within the defined limits.

A CPP can be controlled by in-process controls, Process

Analytical Technology (PAT), or by operating conditions that

are themselves controlled by system (equipment) parameters

under monitoring or metrology and maintenance plans.

The critical input and in-process material attributes can

be controlled by analytical testing such as assays, tests, char-

acterization tests (identity, purity, stability). It is the set of

in-process materials control and process parameters control

that ensure, as a whole, the CQAs.

To summarize, a CQA can be ensured by the combination

of several controls:

- End product release testing (content of impurity X)

- End product characterization (i.e., molecular profiles,

amino acid sequences, biochemical assays, physicochemi-

cal composition, conformation, purity. Characterization

tests are usually used for product comparability dem-

onstration after change)

- Input material testing for specifications and/or charac-

terization (content of impurity X in intermediate n°1,

before IEC step; IEC medium specified and checked)

- Manufacturing process operation control (implicit in

the design of the process, respect of the operations and

their order)

- In-process controls including:

> process parameters monitoring – 1. linear flow rate

monitoring continuously during the process; 2. check

of parameters, and 3. once per batch

> in-process material testing (content of impurity X in

intermediate n°2, after IEC step)

> Critical System Parameters (CSP – parameters

directly linked to the equipment technology, pro-

cess scale, and operating mode) control, including

monitoring, trends, records of operating conditions

ensuring the CPPs (pressure, temperature continuous

monitoring, column efficiency verification after each

batch)

> Maintenance, calibration to ensure the reliability of

the data recorded (pressure and temperature mea-

surements systems verification each month)

All the controls identified during the quality risk assessment

must be gathered for each CQA to be controlled. This set of

controls, classified as product control, material control, process

or systems control constitutes the Control Strategy as soon

as they take part of a CQA control, whatever it is directly or

indirectly. Rationales of Control Strategy must be provided:

the methods, frequency, acceptance criteria of each control

must be scientifically justified. Example of Control Strategy

elements for IEC process is given in Table C.

If the approach is driven to a step forward, the variability

could be totally controlled by the process and the end product

testing could disappear or be minimized, shifting controls

upstream, in-line or at-line, thanks to design space(s), to

real-time release testing, and to in-process controls (including

in-process tests and process parameters). Any alternative ap-

proach to the end product testing, shifting controls upstream,

must provide at least the same level of product quality as-

surance, and ensure that no downstream factor can impact

the CQA.

To conclude, to allow this indirect control of a CQA, mini-

mizing the need for end product testing, an enhanced product

and process knowledge and understanding of the sources of

variability and their impact on downstream process steps,

intermediates and final product is required, combined with

quality risk management. An example of links between

product and process knowledge and understanding and

CQA Process Step Material ID Unit Operation MATs (IEC) Initial Risk Level

Content of Impurity X IEC Intermediate No. 1 1 Impurity X content ≤ 2.0% Medium

Intermediate No. 2 2 Impurity X content ≤ 0.2% High

IEC Medium 3 Medium characteristics Medium

Table A. Material Attributes (MAs).

ID Unit Operation CPP (IEC) CQA Impacted Initial Risk Level

1 Linear �ow rate Content of impurity X

High

2 Protein load volume/column volume ratio

Low

3 Column bed height Low

The process parameters of IEC are (1) Linear �ow rate, (2) Protein load volume/column volume ratio, (3) Column bed height. (1) Linear �ow rate presents high level of risk for this CQA.

Table B. Process parameters.

Control Strategy


Control Strategy elements in a Quality by Design approach

are described in Figure 4.

The Control Strategy is generally established during

product and process development, initially implemented for

production of clinical trial batches to insert its description

for initial submission of the regulatory file. Enhancement of

product and process knowledge at each step of the lifecycle

of the product needs continual improvement of the Control

Strategy to guarantee the attempted quality of the prod-

uct.

Submission of Control StrategyAfter establishing the Control Strategy, a detailed description

of all the means and individual elements to control each CQA

must be presented in the submission file, in accordance with

the regional regulatory requirements.

Control Strategy and its justification are one of the mini-

mum elements to present in the Chemistry Manufacturing

and Controls (CMC) part of the file for its evaluation by the

FDA authorities.12

Regarding the file in CTD format (ICH M4Q13), the local-

ization of data concerning the Control Strategy are so far

not-well established. As proposed by ICH Q11, the data should

be separated in different sections. This breakdown of the

Control Strategy elements can be understood by the previous

explanation of the Control Strategy design: CQA control can

be a combination of elements derived from product control

and others linked to in-process controls, addressed in various

sections of the file in CTD format.

The overview of the overall Control Strategy of the Drug

Substance (DS) can be provided in 3.2.S.4.5 (3.2.P.5.6 for

drug product), an analytical section devoted to justifying

the specifications (release criteria). The enhanced Control

Strategy enables scientific justifications in this section for

the methods frequency and acceptance criteria.

In addition, the detailed information about the individual

elements of the Control Strategy should be described in the

devoted CTD section. Figure 5 shows an example of the links

between the different CS elements and their localization in

the file.

Table C. “Content of impurity X” CS elements.

CQA Process Step Material Initial Risk Level Unit Operation MATs (IEC) Residual Risk

Content of Impurity X

IEC Intermediate No. 1 Medium Impurity X content ≤ 2.0% Low

Intermediate No. 2 High Impurity X content ≤ 0.2% Medium

IEC Medium Medium Medium attributes to be speci!ed and checked

Low

Linear Flow Rate High Continuous monitoring of linear "ow ratePressure and Temperature continuous monitoringColumn ef!ciency veri!cation after each batchMaintenance, Calibration on measurement systems

Low

Protein load volume/column volume ratio

Low Check of parameter once per batch Low

Column bed height Low Check of parameter once per batch Low

Figure 4. Designing a Control Strategy based on the Quality by

Design approach.

Figure 5. Synthesis of one CQA Control Strategy (drug substance)

and example of localization in the �le in CTD format.


Control Strategy

For the Drug Substance (DS): description of manufacturing

process and process controls (3.2.S.2.2), control of materi-

als (3.2.S.2.3), controls of critical steps and intermediates

(3.2.S.2.4), drug substance specification (3.2.S.4.1), container

closure system (3.2.S.6). The evolution of the Control Strategy

should be described in the manufacturing process develop-

ment section of the application (3.2.S.2.6).

For the Drug Product (DP): description of manufacturing

process and process controls (3.2.P.3.3), controls of critical

steps and intermediates (3.2.P.3.4), control of excipients

(3.2.P.4.1 and 3.2.P.4.4), drug product specification (3.2.P.5.1),

container closure system (3.2.P.7). The evolution of the Control

Strategy should be described in the manufacturing process

development section of the application (3.2.P.2.3).

Additional information linked to evaluation, justification,

and future improvement of Control Strategy should be included

in the manufacturing process development section (3.2.S.2.6

for DS and 3.2.P.2.3 for DP).

Proposal for future management of changes to process

parameters and controls is a key for the regulatory flexibility

promised to be offered by Quality by Design development

approach.

Control Strategy as theKeystone of Product Lifecycle

According to ICH guidelines Q8, Q9, Q10, and Q11, the lifecycle

of Control Strategy is supported by pharmaceutical develop-

ment (QbD and initial knowledge management), Quality

Risk Management (QRM), and the Pharmaceutical Quality

System (PQS). Initially developed and implemented during

product development for production of clinical trial materials,

Control Strategy must be refined when new product/process

knowledge is gained during manufacturing of the commercial

batches - Figure 6. This improvement helps maintain the link

between Control Strategy and product/process understand-

ing. In addition, it helps to optimize the analytical methods

by implementation of technical innovations.

Effectiveness of the Control Strategy is checked by the

first step of process validation (process qualification) per-

formed during technology transfer. Control Strategy (CS)

gives the targets for process validation14 requirements

and comparability acceptance criteria.15 Indeed, during

pharmaceutical development, the process design identifies

the significant sources of variability. It implements control

points and methods to take into account the variabilities

and detect their effect, establish the appropriate alert and

action limits to ensure that the product CQAs specifications

will be achieved. Technology transfer receives these inputs

to design and implement the appropriate technologies that

answer to the product and process needs and implement

the CS. Process validation uses the CS elements (“process

controls” type and “product controls” type elements) to dem-

onstrate the process control and the product quality through

appropriate acceptance criteria based on the understanding

of the product/process links.

During the commercial manufacturing step of product

lifecycle, Control Strategy appears as a mandatory enabler

component for implementation of continual improvement

performed under the pharmaceutical quality system. De-

termining the content of the continuous process verification

and providing the components and targets of the product

and process monitoring,14 the Control Strategy sets the path

allowing the implementation of continual improvement. Both

product and Control Strategy lifecycles are closely linked.

On the basis of relevant information provided by data trends

collected over time on target parameters and material attri-

butes, the continual product quality can be performed using

continous process verification to check Corrective Action

Preventive Action (CAPA) and change consequences.9 In a

feedback process, the continuous process verification is a key

component assuring the ongoing effectiveness of the Control

Strategy.

The knowledge gained during product lifecycle on the

relevant product/process components enables continual

Figure 6. Linkage between product and Control Strategy lifecycles.

Control Strategy


5. ICH – Development and Manufacture of Drug Substances

(Chemical Entities and Biotechnical/Biological Entities)

Q11 (step 2), 2011.

6. Nasr, M., “Pharmaceutical Quality for the 21st Century,”

2nd Annual QbD Conference in Israel, 2010.

7. Rathore, A., and Winkle, H. “Quality by Design for Bio-

pharmaceuticals,” Nature Biotechnology, January 2009,

Vol. 27, No. 1, pp. 26-34.

8. ICH – Quality Risk Management Q9, 2005.

9. ICH – Pharmaceutical Quality System Q10, 2008.

10. “Implementation of ICH Q8, Q9, Q10, How ICH Q8, Q9,

Q10 Guidelines Are Working Together Throughout the

Product Lifecycle,” ICH Workshop Washington, D.C.

Workshop, 2010.

11. ICH – Quality Implementation Working Group – “Points

to consider – ICH-Endorsed Guide for ICH Q8/Q9/Q10

Implementation,” 2011.

12. FDA – CDER – Applying ICH Q8 (R2), Q9 and Q10 Prin-

ciples to CMC Review. MAPP 5016.1. 2011.

13. ICH – The Common Technical Document for the Registra-

tion of Pharmaceuticals for Human Use: Quality - M4Q

(R1), 2002.

14. FDA – CDER/CBER/CVM, “Process Validation: General

Principles and Practices,” 2011.

15. ICH – “Comparability of Biotechnological/Biological Prod-

ucts Subject to Changes in Their Manufacturing Process,”

Q5E. 2004.

About the AuthorsJohanne Piriou obtained her MSc in bio-

technology and biochemistry engineering

at National Institute of Applied Sciences of

Lyon (France) in 2004. She joined Aktehom

in 2006 as consultant in pharmaceutical

processes control and improvement. She has

been involved in transfer technology projects

and production start-up of new facilities, as

specialist in process design and validation, and knowledge

transfer to operational teams. She is senior consultant at

Aktehom, specializing in operational implementation of

Quality by Design approaches and parenteral drug products

manufacturing.

Aktehom, 3 avenue Gallieni, 92000 Nanterre, France.

Bernard Elissondo, PhD obtained his

PhD in organic chemistry at the university

of Bordeaux (France) in 1983. He joined the

pharmaceutical industry in 1984, first as

head of analytical development and then

as R&D manager. After 12 years experience

working in the phamaceutical industry, he

became a consultant in the CMC area. Based

on his broad experience covering CMC technical and leader-

ship roles, he specializes in biotechnological and biological

products, particularly in the operational implementation of

Quality by Design and its regulatory submission. He is now a

Aktehom partner and Scientific Director in charge of product

improvement and the maintenance of the Control Strategy,

which can be adapted, particularly through update of process

models, to the real risks and variability concretely met during

manufacturing.

ConclusionControl Strategy is required irrespective of the development

approach, whatever the process situation toward the Qual-

ity by Design approach. It should be defined whether the

process/product has been or is being characterized by a QbD

approach or the product/process has been developed through

a traditional approach.

Every drug substance manufacturing process, whether

developed through a traditional or an enhanced approach,

should have an associated Control Strategy, which can be

designed thanks to a combination of both approaches depend-

ing on the CQAs and their risk level on patient safety and

product efficacy.

Control Strategy includes different types of control to

assure product quality such as in-process controls and end

product testing. For products developed following the minimal

approach, the Control Strategy is usually derived empirically

and typically relies more on discrete sampling and end product

testing. Thanks to product and process characterization under

QbD, the Control Strategy is derived using a systematic science

and risk-based approach. Risk assessments allow the identi-

fication of targets to control among process parameters and

in-process materials attributes. These targets are controlled

through the elements of the CS. The control points can be

shifted earlier into the process and conducted in-line, on-line,

or at-line, as the downstream process steps are characterized

and understood for their potential additional impact on the

final CQAs.

Control Strategy overview, detailed scientific justification

and rationales of each individual element are presented in

the submission file. The continual improvement of Control

Strategy is tightly linked to product lifecycle and continual

improvement of the product quality, enabled by the phar-

maceutical quality system, quality risk management, and

knowledge management processes.

References1. ICH Workshop Washington, D.C. Workshop – Breakout

B: Control Strategy, 2010.

2. Davis, B., Lundsberg, L. and Cook, Graham, “PQLI Control

Strategy Model and Concepts,” Journal of Pharmaceutical

Innovation, 2008,Vol. 3, No. 2, pp. 95–104, www.ispe.org.

3. ISPE Guide Series: Product Quality Lifecycle Implemen-

tation (PQLI®) from Concept to Continual Improvement,

International Society for Pharmaceutical Engineering

(ISPE), First Edition, November 2011, www.ispe.org.

(QbD): Concepts and Principles, including Overview,

Criticality, Design Space, and Control Strategy

(QbD): Illustrative Example

4. ICH – Pharmaceutical Development Q8 (R2), 2009.


Control Strategy

development with a special focus on Scientific and Regula-

tory Affairs. Author of more than 20 publications, Elissondo

is a member of PDA. He can be contacted by email: bernard.

[email protected].


Michel Hertschuh obtained his Msc in

science and manufacturing engineering and

joined the consulting company Alphatem in

1995 as business responsible. He continues to

have account manager responsibility at Assys-

tem in the parenteral area. He is a partner and

co-founder of Aktehom, founded in 2005. Since

then, he has assumed the responsibilities of

development and capitalization and is now Head of Technical

Operations. He has spent his entire career in consulting ser-

vices, primarily for pharmaceutical companies. His expertise

is around the aseptic processes, technology transfer, start-up

production, and regulatory compliance. He can be contacted

by email: [email protected].


Roland Ollivier, PhD obtained his PhD in

organic chemistry at the University of Brest

(France) in 1981. He worked in different phar-

maceutical groups first as chemistry depart-

ment director and then as R&D manager of

the CNS Ddepartment. After 15 years in the

pharmaceutical industry, he became manager

of two societies specializing in the manage-

ment of clinical studies and biological screening of drugs in

the psychotropic and dependence domains. He is currently the

Scientific Manager at Aktehom and specialized in regulatory

compliance and Quality by Design implementation through

product and process comprehension and risk management

specifically in biotechnological domain. He is the author of

several publications and patents and he has also chaired a

conference in the field of pharmaceutical implementation of the

new ICH concepts (Q8-Q9-Q10) for gene therapy products.


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