PHARMACEUTICALS AND BIOCHEMICALS

APPLICATION NOTE
6.01.00
PHARMACEUTICAL PROCESSING
www.kpatents.com

ACTIVE PHARMACEUTICAL INGREDIENTS (APIS),

RAW MATERIAL
Typical end products
Active pharmaceutical ingredients, excipients, intermediates and raw
material for pharmaceutical drugs

ANTIBIOTICS: Penicillin, Sreptomycin,

Tetracyclines, Antifungals.

BLOOD PRODUCTS: Blood, Plasma,

Serum, Infusion liquids, Sodium chloride,
Glucose.

PROTEINS: Proteins and Protein buffer

solutions.

SYNTHETIC DRUGS

VITAMINS: Ascorbic acid, Ca-Arabonate,

Riboflavin, Vitamin-B, Vitamin-C, Sodium
pantonate.

SYNTHETIC HORMONES

SYRUPS: Concentrated aqueous solutions

of sucrose.

DRUGS OF VEGETABLE ORIGIN: Drugs

and Herbal extracts.

VACCINES

SURGICAL SUTURES AND DRESSINGS:

Glue for human tissues.

SOLVENTS, ACIDS AND BASES

Introduction
The regulatory authority of the Food and Drug
Administration (FDA) is fundamental to the
development and production of pharmaceuticals.
Furthermore, those involved must comply with the
Good Manufacturing Practices (GMPs), a set of
regulations requiring disciplined standard operating
procedures, with comprehensive documentation
covering every step in the manufacturing process.
The K-Patents Process Refractometers are ideal
real-time instruments perfectly suited for the
fulfilment of these requirements. The ability to
measure and control parameters such as Refractive
Index nD contributes significantly to the development
of effective drugs and their efficient manufacturing.

Typical applications

PHARMACEUTICAL CHEMICALS

ACTIVE PHARMACEUTICAL
INGREDIENTS: Actives, Excipients,
Intermediates.

PHARMACEUTICALS AND BIOCHEMICALS

APPLICATION NOTE
6.01.00
PHARMACEUTICAL PROCESSING
www.kpatents.com

FDA Regulations and Validation

FDA regulations require everything to be thoroughly
tested to make sure that the produced drugs meet
set standards. This is called validation. The short
textbook definition of validation is: "Proof of specified
performance". An important part of the validation
process is determining and proving the suitability of
the process instrumentation for its designated
function, and appropriate use by the purchaser.
Therefore, any new instrumentation needs thorough
testing at the laboratory and at pilot plant stages.
After initial lab testing, the K-Patents refractometer
can be subjected to a pilot plant trial, which may
involve a skid manufacturer. Fulfilment of all the test
phases and their careful documentation facilitates
the refractometer installation into the full scale
production process.

Pharmaceutical Process Design

Utilizing PAT
Process design is the conversion of information on
product
formulation
and
requirements
into
manufacturing
knowledge.
Products
and
manufacturing processes should be designed using
science- and risk-based design strategies to manage
variation. To achieve this, integration of Process
Analytical Technology (PAT) principles and tools
during process design is recommended. This will
enhance opportunities to build, maintain and expand
process understanding throughout the product
lifecycle. The product lifecycle includes a period in
production as well as in development. Process
understanding is the foundation in establishing
manufacturing (process selection, methodology,
implementation and practice), process control (realtime control on the basis of measured critical quality
attributes), effective risk mitigation and product
release concepts.
The K-Patents Process Refractometer is the ideal
process control tool in accordance with the PAT
framework. The drug manufacturer can both reduce
development time and improve product reliability
through thorough process analysis. This is possible
using the same refractometer during pilot and
production phases.

FDA Title 21 CFR Part 11 and Datalogging via Ethernet

Title 21 CFR Part 11 of the Code of Federal
Regulations deals with the Food and Drug
Administration (FDA) guidelines on electronic records
and signatures in the United States. Part 11 defines

the criteria under which electronic records and

signatures are considered to be trustworthy, and
equivalent to paper records. Part 11 requires drug
makers, medical device manufacturers, biotech
companies, biologics developers and other FDAregulated industries to implement controls. These
include system validations, audits, audit trails,
electronic signatures, documentation for software
and systems involved in processing electronic data,
which are (a) required to be maintained by the FDA
predicate rules or (b) used to demonstrate
compliance to a predicate rule.
The K-Patents Process Refractometers facilitate the
technical controls necessary for 21 CFR Part 11
compliance.
The K-Patents refractometers have an Ethernet
communication solution, which facilitates electronic
data records for FDA 21 CFR Part 11 adherence.
The transmitter uses the IP protocol to communicate
over the Ethernet to any type of computer. This
eliminates human error and allows for an easy
refractometer
generated
measurement
and
diagnostic data capture for storage, analysis and
reporting.
K-Patents provides a software package for data
downloading. Full software specifications are freely
available for users, who wish to develop their own
communications
program.
Access
to
the
refractometer and the generated data can be
restricted to authorized personnel using password
protection. Together with the user's own procedural
and administrative user controls, compliance with the
21 CFR Part 11 is assured.

Instrumentation
The K-Patents Process Refractometer PR-23 series
offers the pharmaceutical industry many specifically
designed technological advantages.
These include:
- Process wetted materials: Stainless steel AISI316L,
PTFE Teflon, Sapphire, Spinel, EPDM, Viton.
- Pharma mini flow cell PMFC with electro-polished
wetted material (Ra 0.4m/15 inch) for low volume
pharmaceutical and biochemical pilot processes.
- Electro-polished wetted materials to secure surface
roughness of Ra<0.4m/15 inch.
- No animal derived media is used in the polishing
and finishing processes.

PHARMACEUTICALS AND BIOCHEMICALS

APPLICATION NOTE
6.01.00
PHARMACEUTICAL PROCESSING
www.kpatents.com

- Optional sensor models to suit small or large scale

processes: pilot (PR-23-AC, PR-33-S), production
(PR-23-GP/AP).

Instrumentation

Description
FOR LABORATORY, PILOT AND PRODUCTION SCALES:
K-Patents Sanitary Compact Refractometer PR-23-AC for small pipe line sizes of
2.5 inch and smaller.
The PR-23-AC sensor is installed in the pipe bend. It is angle mounted on the
outer corner of the pipe bend directly, or by a flow cell using a 3A Sanitary clamp
or Varivent connection.
FOR PRODUCTION SCALES:
K-Patents Sanitary Probe Refractometer PR-23-AP for installations in large
pipes, tanks, cookers, crystallizers and kettles, and for higher temperatures up to
150C (300 F). Installation through a 3A Sanitary clamp.

FOR PRODUCTION SCALES:

K-Patents Process Refractometer PR-23-GP is an industrial refractometer for
large pipe sizes and tanks, cookers, crystallizers and kettles. Installation through
a flange or clamp connection.

Measurement range:

Refractive Index (nD) 1.3200 1.5300, corresponding to 0-100 Brix.