# f4fa8009-74bf-4296-96d0-8e2539f9a07c

## Metadata

- Author: Prasad Mogalagani

- Category: pdf
- Document Tags: Lauras Labs
- URL:
https://www.bseindia.com/xml-data/corpfiling/AttachLive/f4fa8009-74bf-4296-
96d0-8e2539f9a07c.pdf
\## Highlights

2006 marked the beginning of Laurus Labs' journey. Initially established

as a CRAMS (Contract Research and Manufacturing Services) company, it
quickly ventured into the field of antiretroviral drugs (ARVs) due to
the development of innovative synthetic routes for critical ARV active
pharmaceutical ingredients (APIs). After five years, the Company
significantly bolstered its capabilities and transformed into an
esteemed API company. Another five years down the line, Laurus Labs
further expanded its expertise, evolving into an integrated
pharmaceutical company.

Our goal is to be a research-driven, integrated pharmaceutical company

and with one of the largest research divisions in the industry for APIs,
I can say overlapping the competencies of Research and Manufacturing is
the crux of our success.

Talent acquisition and retaining the talent is a challenge and the

company is investing lot of resources to address this.

massive generic manufacturing hub to a value-adding manufacturing hub

for both Generic and innovative drugs.

s Anti-Retro viral (ARV), Oncology, Cardiovascular and Diabetic

. CDMO segment has obtained a dedicated USD 100 million investment

. There has been more than 28% capacity expansion in small molecules and
CMO pipeline has been increased. A new Sterile Lab has commenced
operations.

continuous flow chemistry Note: Continuous flow chemistry, also known as

flow chemistry or flow synthesis, is a technique used in chemical
synthesis where reactions are performed in a continuous flow of
reactants through a reaction system rather than in batch mode. In batch
chemistry, reactions are typically carried out in a single vessel or
flask, where reactants are combined and allowed to react for a specific
period of time before the reaction is stopped.

In continuous flow chemistry, the reactants are continuously pumped

through a flow reactor, which consists of a series of interconnected
reaction modules or channels. The reactants flow through these modules,
where they mix and react under controlled conditions. The products of
the reaction are then collected at the outlet of the system.

There are several advantages to using continuous flow chemistry compared

to traditional batch chemistry:

1. Improved heat and mass transfer: Continuous flow systems typically

 have a larger surface area-to-volume ratio compared to batch
reactors, allowing for better heat and mass transfer. This can lead
to faster reaction rates, improved selectivity, and the ability to
perform reactions that would be challenging or impossible in batch
mode.

2. Enhanced safety: Continuous flow chemistry allows for better control

over reaction conditions, such as temperature and pressure. This can
minimize the risk of runaway reactions and enable the use of more
hazardous reagents or reaction conditions. Additionally, the small
reaction volumes in flow systems reduce the potential for
large-scale accidents or spills.

3. Precise control and automation: Continuous flow systems can be

easily automated, allowing for precise control of reaction
parameters such as temperature, residence time, and reagent flow
rates. This enables rapid optimization of reaction conditions and
facilitates the synthesis of complex molecules.

4. Access to novel reaction conditions: Continuous flow chemistry

provides the opportunity to explore new reaction conditions that may
not be feasible in batch mode. For example, reactions that require
high temperatures, high pressures, or the use of reactive
intermediates can be more easily controlled and performed safely in
a flow system.

5. Scalability: Continuous flow chemistry is highly scalable, as the

reaction can be easily adjusted by changing the flow rate or the
size of the reactor. This enables efficient scale-up from
laboratory-scale synthesis to industrial production.

Continuous flow chemistry has gained significant interest in both

academia and industry due to its numerous advantages. It has been
successfully applied in various fields, including pharmaceutical
synthesis, fine chemicals production, and materials science. The
technique offers the potential for more efficient, sustainable, and
cost-effective synthesis processes. fermentation- based product
developmen Note: Fermentation-based product development involves
utilizing microorganisms, such as bacteria, yeast, or fungi, to convert
raw materials into desired products through the process of fermentation.
This approach has been employed for centuries in various industries,
including food and beverages, pharmaceuticals, biofuels, and
bioplastics. Here are the key steps and considerations in
fermentation-based product development:

1. Strain selection: Choosing the right microorganism strain is

crucial. Factors to consider include the microorganism's ability to
produce the desired product, its robustness, its tolerance to
process conditions, and its scalability.

2. Substrate selection: Selecting an appropriate substrate or raw

material for fermentation is important. The substrate can be a
variety of organic materials, such as sugars, starches, or
agricultural by-products. The choice of substrate affects the yield,
productivity, and overall economics of the fermentation process.

3. Fermentation process design: Designing the fermentation process

involves determining the optimal conditions for microbial growth and
product formation. This includes parameters such as temperature, pH,
 oxygen availability, nutrient concentrations, and agitation. Process
optimization aims to maximize product yield, minimize unwanted
by-products, and ensure efficient resource utilization.

4. Fermentation vessel design: The choice of fermentation vessel

depends on the scale of production. Small-scale laboratory
fermentations may use flasks or bioreactors, while larger-scale
production may require industrial-scale fermenters. The vessel
design should facilitate efficient mixing, oxygen transfer, and heat
removal.

5. Monitoring and control: Monitoring and controlling the fermentation

process parameters are crucial for achieving consistent product
quality. This involves measuring and controlling variables such as
pH, temperature, dissolved oxygen, and nutrient concentrations.
Automated systems can be employed to ensure real-time monitoring and
precise control.

6. Downstream processing: After fermentation, the product needs to be

separated and purified from the fermentation broth. Downstream
processing techniques such as filtration, centrifugation,
chromatography, and drying are used to isolate and refine the
desired product.

7. Product analysis and quality control: The final product needs to

undergo rigorous analysis to ensure it meets quality specifications.
This may involve testing for purity, potency, microbial
contamination, and other relevant parameters.

8. Scale-up and production: Once the fermentation process has been

optimized at a small scale, it can be scaled up to meet commercial
production demands. Scale-up involves considering factors such as
mass transfer limitations, equipment design, and process economics.

9. Regulatory considerations: Depending on the application and market,

fermentation-based products may need to comply with various
regulatory requirements. This includes obtaining necessary
approvals, adhering to Good Manufacturing Practices (GMP), and
meeting safety and labeling standards.

10. Continuous improvement and innovation: Fermentation-based product

development is an iterative process that involves continuous
improvement and innovation. Feedback from product performance,
market demands, and scientific advancements can drive further
optimization and development of new fermentation processes.

Fermentation-based product development offers a sustainable and

efficient approach to produce a wide range of valuable products. By
harnessing the power of microorganisms, it enables the production of
bioactive compounds, therapeutic proteins, biofuels, flavor and
fragrance molecules, and more. • Proton Pump Inhibitors

Laurus Labs has filed an NDA for a novel HIV paediatric product based on
a new ODF platform

small molecules, including HP APIs, GMP intermediates, chiral chemistry,

peptides, and hazardous chemistry Note: The fields of small molecules,
including HP APIs (High Potency Active Pharmaceutical Ingredients), GMP
(Good Manufacturing Practice) intermediates, chiral chemistry, peptides,
and hazardous chemistry are all important areas in pharmaceutical and
chemical development. Here's an overview of each:

1. Small molecules: Small molecules are organic compounds with a

relatively low molecular weight. They are widely used in drug
discovery and development due to their ability to target specific
biological pathways and receptors. Small molecule drugs can be
synthesized through various chemical reactions and are typically
administered orally or via injection.

2. High Potency APIs (HP APIs): HP APIs refer to active pharmaceutical

ingredients that are potent in small quantities and may have potent
pharmacological effects. These substances require special handling
and manufacturing processes to ensure operator safety and avoid
cross-contamination. Stringent containment measures and specific GMP
guidelines are followed to protect workers and maintain product
quality.

3. GMP intermediates: GMP intermediates are the chemical compounds

produced during the synthesis of an active pharmaceutical ingredient
(API) that require adherence to Good Manufacturing Practices. These
intermediates must meet specific quality standards to ensure
consistency, purity, and safety. GMP compliance ensures that the
intermediates are manufactured in a controlled environment,
minimizing the risk of contamination and ensuring reproducibility.

4. Chiral chemistry: Chiral chemistry involves the study and

manipulation of molecules with non-superimposable mirror images
(enantiomers). Many drugs and compounds used in pharmaceuticals
exhibit chirality, and it is important to control and understand
their stereochemistry. Chiral separation techniques, asymmetric
synthesis, and chiral resolution methods are employed to isolate or
produce specific enantiomers, which can have different biological
activities or pharmacokinetic profiles.

5. Peptides: Peptides are short chains of amino acids linked together

by peptide bonds. They are involved in numerous physiological
processes and have gained significant attention as therapeutic
agents. Peptide drugs can be designed to target specific receptors,
inhibit enzymes, or modulate signaling pathways. Peptide synthesis
often involves solid-phase peptide synthesis (SPPS) and requires
specialized techniques for proper folding and stability.

6. Hazardous chemistry: Hazardous chemistry refers to the handling and

synthesis of chemical compounds that pose risks to human health or
the environment. These compounds may be toxic, flammable, reactive,
or pose other hazards. Proper safety measures, containment
protocols, and engineering controls are essential to mitigate risks.
Hazardous chemistry is prevalent in the development of certain
drugs, agrochemicals, and industrial chemicals.

In each of these areas, adherence to regulatory guidelines, safety

protocols, and quality control measures is of utmost importance. The
development and production of pharmaceuticals and chemicals in these
fields require specialized expertise, appropriate facilities, and
adherence to relevant regulations to ensure efficacy, safety, and
environmental responsibility. Build a bigger moat for CDMO and CMO
service business and capitalise on diversification of outsourcing and
dual sourcing trends
Consolidate ARV share and strengthen global leadership in Oncology, HP
APIs & Scaling up of Anti-diabetic, PPI, and CV portfolio

Drug Master File Note: A Drug Master File (DMF) is a confidential

document submitted to regulatory authorities by a pharmaceutical
manufacturer, typically in support of a new drug application (NDA) or a
generic drug application. A DMF contains detailed information about the
manufacturing, processing, quality control, and stability of a drug
substance, drug product, or excipient.

Here are some key points about Drug Master Files:

1. Purpose: The primary purpose of a DMF is to provide confidential,

detailed information about the manufacturing and control of a drug
or its components. The information in the DMF serves as a reference
for regulatory authorities when reviewing applications for marketing
authorization or generic drug approvals.

2. Confidentiality: DMFs are considered confidential documents, and the

information contained within them is not disclosed to the public.
The DMF is submitted to regulatory authorities but is not part of
the public record. Its confidentiality is maintained to protect
proprietary information and trade secrets of the drug manufacturer.

3. Contents: The specific contents of a DMF can vary depending on the

regulatory requirements of the country or region. However, typical
sections of a DMF may include:

- General information: Manufacturer's name, contact details, and

regulatory references.
- Drug substance or product characterization: Chemical and
physical properties, manufacturing process, and control
strategy.
- Analytical methods: Description of analytical methods used for
testing the drug substance or product.
- Stability data: Data on the stability of the drug substance or
product under various storage conditions.
- Manufacturing process: Detailed description of the manufacturing
process, including equipment, process steps, and controls.
- Quality control: Specifications, analytical procedures, and
validation data for quality control testing.
- Packaging information: Details of the drug product packaging,
including labeling and package inserts.

4. Referencing the DMF: When a drug manufacturer includes a DMF as part

of their application, they provide a letter of authorization to the
regulatory authority, allowing them to reference the confidential
information contained in the DMF during the evaluation of the
application. This allows the manufacturer to protect their
proprietary information while still providing necessary data to
support the application.

5. Regulatory review: Regulatory authorities review the information in

the DMF as part of their assessment of the drug application. They
evaluate the manufacturing process, quality control measures, and
other relevant data to ensure compliance with regulations and
guidelines. The DMF serves as a supporting document to demonstrate
the quality, safety, and efficacy of the drug or its components.
6. DMF Types: There are different types of DMFs, such as drug substance
DMFs, drug product DMFs, and excipient DMFs. Each type focuses on
specific aspects of the drug development and manufacturing process.

DMFs are an important tool in the regulatory process, allowing

pharmaceutical manufacturers to protect confidential information while
providing necessary data to regulatory authorities. They streamline the
review process by separating proprietary information from the publicly
available drug application and facilitate efficient evaluation of the
drug's safety, quality, and efficacy. Richcore Life Sciences Pvt Ltd
(Laurus Bio)

Incorporated Laurus Speciality Chemicals Pvt. Ltd. A Wholly Owned

subsidiary of Laurus Synthesis Pvt. Ltd

T:Tenofavir, L: Lamivudine, D: Dolutegravir, Note: The combination of

tenofovir (T), lamivudine (L), and dolutegravir (D) is a commonly used
antiretroviral therapy (ART) regimen for the treatment of HIV infection.
Each of these drugs belongs to a different class of antiretrovirals and
works in different ways to suppress the replication of the human
immunodeficiency virus (HIV). Here's a brief overview of each drug:

1. Tenofovir (T): Tenofovir is a nucleotide reverse transcriptase

inhibitor (NRTI). It inhibits the reverse transcriptase enzyme,
which is necessary for the replication of HIV. Tenofovir is
available in two forms: tenofovir disoproxil fumarate (TDF) and
tenofovir alafenamide (TAF). Both forms are effective in suppressing
HIV, but TAF is associated with lower renal and bone toxicity.

2. Lamivudine (L): Lamivudine is also an NRTI. It acts by inhibiting

the reverse transcriptase enzyme, preventing the conversion of HIV
RNA into DNA. Lamivudine is well-tolerated and has a high genetic
barrier to resistance. It is commonly used in combination with other
antiretrovirals for HIV treatment.

3. Dolutegravir (D): Dolutegravir is an integrase strand transfer

inhibitor (INSTI). It works by blocking the integrase enzyme, which
is responsible for incorporating viral DNA into the host cell's DNA.
By inhibiting this step, dolutegravir prevents the replication of
HIV. Dolutegravir has demonstrated potent antiviral activity and a
high barrier to resistance.

The combination of Tenofovir, Lamivudine, and Dolutegravir (TLD) has

shown excellent efficacy and tolerability in the treatment of HIV
infection. It is recommended as a first-line regimen in many treatment
guidelines worldwide. TLD offers a convenient once-daily dosing regimen
and has been associated with a low risk of drug resistance development.

It is important to note that specific treatment regimens and drug

combinations may vary based on individual patient factors, such as viral
resistance patterns, comorbidities, and drug-drug interactions. HIV
treatment decisions should always be made in consultation with a
healthcare professional who can consider the patient's specific needs
and optimize their antiretroviral therapy. CAR-T (Chimeric Antigen
Receptor T-cell) technology is a type of immunotherapy that uses a
patient's own immune system to fight cancer. It involves taking T cells
(a type of white blood cell) from a patient's blood and modifying them
in a laboratory to produce chimeric antigen receptors (CARs) on their
surface. These CARs can then identify and bind to specific proteins on
cancer cells, leading to the destruction of the cancer cells by the
patient's immune system. The modified CAR-T cells are then infused back
into the patient's bloodstream, where they multiply and continue to
attack cancer cells. CAR-T therapy has shown promising results in
treating certain types of cancer, particularly in patients who have not
responded to other treatments.

The Company's CAPEX plans for this plant are focused on expanding their
manufacturing capabilities for animal health and Crop Science
ingredients at their Visakhapatnam site (LSPL-U2 and LSPL-U4).

precision fermentation and recombinant DNA technology,

60+ active projects (Phase I, II and III +\

CMO).

10+ Commercial projects (4 APIs and\

several intermediates)

+28% Capacity expansion in small\

molecules manufacturing reactor volume to 7.5 million litre

Laurus Labs is following disciplined approach to investments in

disruptive technologies with goal to invest up to 10% of profits. These
could be across innovative treatments such as Cell and Gene therapy
(CGT), New process devices, New drug delivery platform like Oral
disintegrating films (ODF) and Automation. We will act when the
scientific opportunity and the value aligns together

• Filed NDA for novel HIV pediatric\

product based on new DP platform in ODF. Additionally, the platform is
being explored to create innovative pipeline in other wide range of
therapeutics

Developing novel enzymes and biotransformation tech

505b(2) products Note: A 505(b)(2) product refers to a regulatory

pathway under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic
Act in the United States. It provides an alternative route for the
approval of a new drug application (NDA) that relies, in part, on data
from studies previously conducted for an already approved drug. Here's a
summary of 505(b)(2) products:

1. Background: The 505(b)(2) pathway was established to streamline the

drug approval process by allowing sponsors to reference existing
data and information for an approved drug, while still requiring the
submission of additional data to support the changes or
modifications being made.

2. Rationale: The 505(b)(2) pathway is utilized when a drug does not

meet the criteria for a completely new drug application (NDA) or an
abbreviated new drug application (ANDA). It is typically used for
modifications or changes to an existing drug, such as:

- New indications or formulations

- Different dosages or routes of administration
- Changes in dosage forms or strengths
- Reformulations or combinations of approved drugs
- Changes in labeling or safety information

3. Data Requirements: The 505(b)(2) application requires the submission

of data that bridge the differences between the proposed product and
the referenced approved drug. This may include:

- Clinical data: Additional clinical trials may be needed to support

the changes being made, such as demonstrating safety, efficacy, or
bioequivalence for the modified drug product.

- Literature data: Existing published literature or scientific

literature can be referenced to support the proposed changes.

- Published studies: Studies conducted by others can be used, with

appropriate permissions and references, to support the proposed
changes.

4. FDA Review Process: The FDA reviews 505(b)(2) applications in a

similar manner to NDAs but with a focus on evaluating the
modifications or changes being made compared to the referenced drug.
The FDA considers both the new data provided and the reliance on
existing data from the referenced drug to assess the safety,
efficacy, and quality of the proposed product.

5. Benefits: The 505(b)(2) pathway offers advantages compared to a full

NDA because it leverages existing data, potentially reducing the
time and cost of drug development. It also allows for modifications
or improvements to existing drugs, bringing new treatment options to
market without repeating extensive preclinical and clinical studies.

6. Examples: Examples of products that can be developed through the

505(b)(2) pathway include modified-release formulations of existing
drugs, drugs with new indications, or drugs reformulated for
pediatric use. The pathway is particularly useful when a drug's
intellectual property has expired, allowing for modifications and
improvements while maintaining some level of exclusivity.

The 505(b)(2) pathway provides a regulatory framework that facilitates

the development and approval of modified or improved drugs by allowing
sponsors to leverage existing data. It promotes innovation while
ensuring safety and efficacy through the submission of additional
information as required by the FDA. Acquired 26% Stake in Ethan Energy\
India Pvt. Ltd to boost captive renewable power

Invested into Green Chemistry Platforms - Bio-enzyme catalysis and

Continuous flow chemistry

pharma companies must prioritize operational restrategizing, digital

acceleration, advanced analytics, product innovation, and developing
solutions for testing and critical care.

Pharmaceutical companies are reconsidering supply chain and

manufacturing decisions, focusing on operational strategy to address
long-term externalities like high inflation and increasing risk factors.
These challenges add to persistent pricing pressures, especially in
generics. Amidst these circumstances,
Price competition, at times, results in relaxed manufacturing standards
and hence sub-standard quality products, resulting in increasing number
of generic medicine recalls.

New opportunities in emerging markets especially Africa has scope for

high growth. This is reflected mainly due to rapid urbanization,
improvement in infrastructure of logistics, increasing investment in
healthcare sector, rising consumer demand, geopolitical stability and
regulatory changes.

According to the Indian Economic Survey 2023, the Indian pharmaceutical

market is expected to triple in the coming decade. India's domestic
pharmaceutical market stood at USD 48 billion in 2022 and is likely to
reach USD 65 billion by 2024 and further expand to reach USD 120-130
billion by 2030, growing at a CAGR of almost 22.4%. The Indian
biotechnology industry, comprising of biopharmaceuticals, bio-services,
bio-agriculture, bio-industry and bioinformatics, was valued at USD 70.2
billion in 2020 and is expected to reach USD 150 billion by 2025. India
is also the second largest in the world in terms of manpower in the
pharmaceutical and biotech sector. In FY2022, the country generated a
trade surplus of USD 15.8 billion in the sector.

India is the world's largest supplier of generic medications, accounting

for 20% of the worldwide supply by volume and supplying about 60% of the
global vaccination demand. Indian drugs are exported to more than 200
countries in the world, with the US as the key market.

Dependence on imports for intermediates

Emergence of new hubs for generic drug manufacturing

Laurus is one of the world's leading suppliers of anti-retroviral APIs

and intermediates. The low-cost technologies in this critical segment
are enabling access to affordable medicine for patients across the
globe.

Oncology is another one of the Company's core competencies and offers a

comprehensive range of APIs in this segment. The state-of-the-art
facilities at Laurus Labs are capable of handling high-potent materials
at both development and commercial scale. Laurus Labs is continuously
extending its portfolio by focusing on molecules in diabetes,
ophthalmology, and cardio-vascular therapy areas, endeavouring to
establish a leadership position.

Laurus Bio -- Recombinant products -- animal origin free products for

safer and viral free bio manufacturing

The Indian API industry, which has an estimated size of \` 1,000- 1,100
billion in FY2023 is expected to grow at a CAGR of 7% to 8% over the
next three to four years, attributing this growth to several factors
like increasing geriatric population, growing prevalence of chronic
diseases and increasing demand for contract manufacturing with global
customers looking to diversify their supply chain dependence from China
to alternative destinations

Extensive experience in handling manufacture of Highly-Potent (Cytotoxic

and Steroidal Hormones) APIs & Intermediates both at Pilot scale &
commercial scale ; Dedicated cGMP Containment manufacture capability at
all scales and across multiple sites.
Conventional column chromatography capability laboratory, pilot and
commercial scale; Adequate preparatory HPLC expertise & capacities:
Lab-scale (100ml /min) to pilot scale (1000ml/ min) (Agilent & Knauer) &
Column packers (Novasep & Asahi Kasei); Pilot scale to commercial scale
SMB installations - Novasep varicol 6X50mm @ pilot-scale & 5X300mm @
commercial-scale

Laurus Labs has established a leadership position for itself in the

manufacture and supply of nature identical and highly-pure polyphenols
(Curcumin, Resveratrol and Pterostilbene etc). It has developed
technologies for several key ingredients including carotenoids
(Beta-carotene, Astaxanthin), Huperzine A and novel nutraceutical
co-crystals of Pterostilbene, Caffeine and Curcumin with enhanced
bioavailability and controlled absorption properties.

The Synthesis division also offers Contract Development and

Manufacturing services (CDMO) for Global Nutraceutical clientele through
contract manufacturing that conform to the international compliance
standards prescribed by GMP, Kosher, Halal and HACCP. With manufacturing
efficiency and quality rigor that match those of the pharmaceutical
APIs, the Ingredients business has gained a reputation for consistent
quality and supply assurance.

By harnessing the power of precision fermentation and synthetic biology,

the Company is paving the way for a global shift away from
animal-derived products and making medicines and food, safer and more
sustainable. The corporate goals are aligned with the goals of the
society at large to achieve meaningful and sustainable economic
development.